key: cord-0683644-x2h0w8u5 authors: Biermann, Ursula; Bornscheuer, Uwe T.; Feussner, Ivo; Meier, Michael A. R.; Metzger, Jürgen O. title: Fatty Acids and their Derivatives as Renewable Platform Molecules for the Chemical Industry date: 2021-05-01 journal: Angew Chem Int Ed Engl DOI: 10.1002/anie.202100778 sha: b1a62c1121f0e1d94d2352e6cdef7c9c5e11bd4e doc_id: 683644 cord_uid: x2h0w8u5 Oils and fats of vegetable and animal origin remain an important renewable feedstock for the chemical industry. Their industrial use has increased during the last 10 years from 31 to 51 million tonnes annually. Remarkable achievements made in the field of oleochemistry in this timeframe are summarized herein, including the reduction of fatty esters to ethers, the selective oxidation and oxidative cleavage of C–C double bonds, the synthesis of alkyl‐branched fatty compounds, the isomerizing hydroformylation and alkoxycarbonylation, and olefin metathesis. The use of oleochemicals for the synthesis of a great variety of polymeric materials has increased tremendously, too. In addition to lipases and phospholipases, other enzymes have found their way into biocatalytic oleochemistry. Important achievements have also generated new oil qualities in existing crop plants or by using microorganisms optimized by metabolic engineering. Oils and fats of vegetable and animal origin are historically and currently the most important renewable feedstock of the chemical industry.I nG ermany,t he chemical industry used about 2.6 million tonnes (Mt) of renewable feedstock in 2018. Thereof,about 1.17 Mt (46 %) consisted of oils and fats used for the production of surfactants and cosmetics (56 %), paints and coatings (7.2 %), lubricants (4 %), polymers (15 %) , adhesives,and others (17.8 %) . [1] Classic oleochemistry preferentially deals with the chemistry of the carboxy group of fatty acids.Some reactions across the C-C double bond, such as hydrogenation, epoxidation, and ozonolysis are performed industrially as well. [2] During the last decades,modern organic chemistry,including enzymatic and biotechnological methods,w as introduced to fatty acid chemistry. [3, 4] In the first decade of this century, important advances were made in the application of homogeneously and enzymatically catalyzed reactions applied to fatty compounds as well as microbial transformations.F at-based monomers were more frequently used for polymer synthesis. [4] Classic plant breeding as well as metabolic engineering was applied to improve natural oils and fats significantly,i nsofar as they show am ore uniform and often unusual fatty acid spectrum, adjusted for various applications. Moreover,m icrobial oils provide interesting substrates such as 3a, 15 a,a nd 16 a for chemical and biological syntheses.A broad spectrum of long-chain fatty acids,esters,and alcohols is available for oleochemical applications (Scheme 1). We herein report the advances made in the chemistry and biotechnology of fatty compounds as well as improvements in Oils and fats of vegetable and animal origin remain an important renewable feedstock for the chemical industry.Their industrial use has increased during the last 10 years from 31 to 51 million tonnes annually.R emarkable achievements made in the field of oleochemistry in this timeframe are summarized herein, including the reduction of fatty esters to ethers,t he selective oxidation and oxidative cleavage of C-C double bonds,t he synthesis of alkyl-branched fatty compounds,the isomerizing hydroformylation and alkoxycarbonylation, and olefin metathesis.The use of oleochemicals for the synthesis of agreat variety of polymeric materials has increased tremendously,too.Inaddition to lipases and phospholipases,o ther enzymes have found their way into biocatalytic oleochemistry.I mportant achievements have also generated new oil qualities in existing crop plants or by using microorganisms optimized by metabolic engineering. the production of natural oils and fats in plants and microbials within the last ten years. Theannual global production of the major vegetable oils (palm and palm kernel, coconut, soybean, rapeseed, cotton, peanut, sunflower,a nd olive oil) increased by 47.8 %t o 208.1 Mt in 2019, [5] compared to 140.8 Mt in 2009. [6] In addition, about 27.4 Mt of animal fats (tallow,l ard, butter, and fish oil) were produced, am oderate increase of 16 % compared to 2009. Thea nnual global production of oils and fats suitable as oleochemical feedstock is shown in Figure 1f or 2009 and 2019. Palm oil showed the most significant growth of 68 %, followed by soybean oil of 57 %, sunflower oil of 56.5 %, and palm kernel oil of 56 %, whereas rapeseed oil and tallow showed am oderate increase of 15 %a nd 19 %, respectively. Castor and linseed oil, providing fatty acids 7a and 5a, respectively,a re almost exclusively used by oleochemistry. Thep roduction of these oils increased by 23 %a nd 30 %, respectively. In 2020, this steadily increasing trend in the global oils and fats production surprisingly reversed. Thep roduction decreased by 2.2 Mt (À0.9 %) and consumption decreased by 1.7 Mt (À0.7 %). [5] Especially the production of palm oil displayed ad owntrend by 2.3 Mt (À3.0 %), because of previous dryness,r educed fertilizer application provoked by the low palm oil prices in 2019, and agrowing share of the oil palms being older than 20 years with declining yield potential. Thus,the yield of palm oil fell in Indonesia from 3.43 tha À1 in 2019 to 3.35 tha À1 in 2020. However,a lso effects of the COVID-19 pandemic are curbing the production, and especially the consumption, because of the worldwide lockdowns in 2020. Palm oil consumption declined by 2Mti n2 019/20, Ursula Biermann studied food chemistry in Hannover and Munich (Germany). She received her Ph.D. in 1979 at the Technical University of Munich. Since 1987, she has been aresearch fellow at the Institute of Chemistry of the University of Oldenburg under the direction of J. O. Metzger,w here she worked on the synthesis of novel fatty compounds using natural oils and fats as chemical raw materials until she retired in 2018. Uwe T. Bornscheuer studied chemistry and received his Ph.D. in 1993 at Hannover University (Germany) followed by apostdoc at Nagoya University (Japan He is chairman of abiosus e.V., anon-profit associationf or the advancemento fresearch on renewabler aw materials. His research areas include sustainability in chemistry,and fats and oils as renewabler aw materials. mainly in the food and biodiesel sector;this is the first decline in palm oil statistics ever recorded. [5] Important to note,inorder to increase the palm oil output in Indonesia and in Malaysia, it will be increasingly necessary to replant oil palms having an improved tha À1 yield and not to depend on area expansion. This requirement is also triggered by sustainability concerns,asdemand in developed countries favors deforestation-free oils and seeks sustainability certifications for vegetable oil used as biodiesel feedstock. Several certification schemes operate and are widely used in Malaysia and Indonesia. [7] Industrial Use:In2009/10, of the globally consumed plant oils totaling 138.5 Mt, about 108 Mt (78 %) were used as food and 31 Mt (22 %) were used industrially for the production of biodiesel, oleochemicals,a nimal feed, and other applications. [8a] In 2019, the food use increased to 150 Mt (74.5 %), industrial use increased to 51 Mt (25.5 %). [8b] Thei ndustrial use of the globally consumed palm oil has more than doubled from 10. Thei ndustrial use of palm oil and palm kernel oil is steadily moving to Southeast Asia, mainly to Indonesia and Malaysia, close to the raw material sources. [4] Thus,i n2 009, 3.1 Mt of palm oil was used industrially in this region, about 30 %o ft he global industrial palm oil consumption of 10.1 Mt. [8a] In 2019, the industrial consumption of palm oil had almost quadrupled to 12.1 Mt, representing 53 %o ft he global industrial palm oil consumption. [8b] In the same time period, the palm kernel oil consumption quadrupled from 0.6 Mt to approximately 2.5 Mt in Indonesia. In Malaysia, palm kernel oil consumption increased moderately from 1.4 Mt to 1.55 Mt in 2019. Thus,the two countries,asthe main producers of palm and palm kernel oil, also accounted for more than 60 %o ft he global palm kernel oil use,p rimarily within their oleochemical industries. [5, 6] Thep roduction of biodiesel increased from ca. 16 Mt in 2009 to 46 Mt in 2019. Scheme 1. Fatty compounds as substrates for synthesis:stearic acid (1a), oleic acid (2a), palmitoleic acid (3a), linoleic acid (4a), alinolenic acid (5a), erucic acid (6a), ricinoleic acid (7a), petroselinic acid (8a), gondoica cid (9a), sterculic acid (10 a), dihydrosterculic acid [6] and 2019. [5] Figure 2. Global industrial consumption of plant oils for biodiesel, [5] oleochemicals, animal feed, and other applicationsin2019. [8b] Them ain feedstock was palm oil, followed by soybean and rapeseed oil ( Figure 2 ). [5] Remarkably,i n2 009 Indonesia produced 0.4 Mt (2.5 %) and in 2019 7.5 Mt (16 %) of biodiesel. Used cooking oil is ag rowing feedstock and contributed about 11 %t ot he global production in 2019, even 18.6 %int he EU ( Figure 2 ). Reactions, and Platform Chemicals Thes tudy of reactions of fatty compounds to provide interesting low molecular weight products by using modern synthetic, especially catalytic methods has developed tremendously during the last ten years.Especially fatty esters 2b and 17 b were used as model compounds to study the scope of new catalysts for reactions across the internal and terminal C-C double bond, respectively.S ynthetic transformations for the valorization of fatty derivatives were recently reviewed, [9] as well as catalytic approaches to monomers based on renewables and especially fats and oils, [10] and functional selfassembled lipidic systems derived from renewable resources. [11] Theu se of oils and fats as fuel and the necessity of improving the fuel properties has stimulated numerous studies on their catalytic deoxygenation to alkanes and alkenes. [12] Electroorganic synthesis has been applied for biofuel synthesis from fatty acids and triglycerides, [13] and the synthetic potential of Kolbe and non-Kolbe electrolysis of fatty acids has been broadly discussed. [14] 3.1.1. Thehydrogenation of fatty esters to alcohols is efficiently promoted by pincer-type catalysts of inter alia Ru, [15] Os [16] and, more recently,first-row transition metals [17] such as Co [18] or Mn. [19] Most importantly,the acceptorless dehydrogenating coupling of alcohols to esters can be catalyzed as well, [20] as shown by the one-pot, two-step synthesis of wax ester 18 by consecutive hydrogenation-dehydrogenation reactions of 2b using the readily available precatalyst C (Scheme 2). [21, 22] 3.1.2. Reduction to Ethers and to Amines Thereduction of fatty esters allows an easy access to fatty ethers avoiding the competitive reduction to alcohols. InBr 3 , [23] GaBr 3 , [24] Fe(CO) 5 , [25] and potassium tetrakis[(3,5trifluoromethyl)phenyl]borate [26] have been used as catalysts with preferentially tetramethyldisiloxane (TMDS) as the reductant to perform this reaction. Ther eduction of 2b,f or example,u sing GaBr 3 /TMDS without any solvent showed complete conversion of 2b and 89 %y ield of ether 19 (Scheme 3). [24] Remarkably,t riglycerides were reduced to glyceryl trialkylethers [27] and long-chain polyesters to the respective polyethers. [28] Hydrogenation of fatty acids or esters in the presence of an alcohol and catalyzed by Ru/triphos and aLewis acid, such as Al(OTf) 3 , [29] or aBrønsted acid, such as trifluoromethanesulfonimide,g ave the respective fatty ether in ay ield of up to 83 %(Scheme 4). [30] Because all C-C double bonds are hydrogenated, rapeseed oil, which consists of various unsaturated C18 fatty acids, can be directly converted with, for example,butanol to ether 20.T he catalyst Ru/triphos/HNTf 2 also enabled the selective N-monoalkylation of av ariety of primary and secondary amines with triglycerides such as sunflower oil (Scheme 5). [31] 1-O-monoalkyl ethers of glycerol were obtained with high selectivity by catalytic reductive alkylation of fatty acids with glycerol using Pd/C as the catalyst and an acid ion-exchange resin as the cocatalyst. (Scheme 6). [32, 33] 3.2. Reactions Across the C-C Double Bond of Unsaturated Fatty Compounds 3. Ester 2b was oxidized to methyl 9(10)-ketostearate 25 in 85 %yield by aco-catalyst-free Wacker oxidation employing oxygen as the re-oxidant and utilizing PdCl 2 in dimethylacetamide (DMAC) (Scheme 7). [34] Furthermore,w hen benzoquinone/Fe(phthalocyanine) was used as acocatalyst for the reoxidation of Pd, the reaction could be performed at room temperature and 1bar O 2 to give 25 in 79 %yield. [35] Ketone 25 was also obtained by rearrangement of epoxide 24 catalyzed by acidic resins (Scheme 7). [36] Methyl 12-ketostearate was obtained by Pd-catalyzed isomerization of the homoallylic alcohol 7b. [37] Remarkably,analdehyde-selective Wacker-type oxidation allowed the oxidation of 17 b to methyl 11-oxoundecanoate with 79 %selectivity. [38] 3.2.1. Thee poxidation of unsaturated fatty compounds has recently been reviewed with an emphasis on catalytic [39] and chemoenzymatic epoxidation. [40] Follow-up products of fatty epoxides,especially cyclic carbonates,are of steadily increasing importance,f or example,a sp lasticizers [41] and as monomers for non-isocyanate polyurethanes (NIPUs). Thec atalytic transformation of epoxides to carbonates was recently reviewed. [42] Werner et al. developed ah igh-yielding transformation of fatty epoxides to the respective cyclic carbonates under mild reaction conditions using metal catalysts such as CaI 2 /dicyclohexyl 18-crown-6 (27) [43] as well as organocatalysts such as phenolic phosphonium salts. [44] Mono-, di-, and triepoxides as well as epoxidized triglycerides could be transformed with high conversion and yield, however, with low diastereoselectivity.F or instance,t he cis-configured epoxide 24 yielded am ixture of cis-a nd trans-carbonate 26 (Scheme 8). [43] Kleij et al. reported ap rotocol using ab inary Al complex/bis(triphenylphosphine)iminium chloride catalyst and obtained cis-26 with high diastereoselectivity (97:3). [45] 3. Theozonolysis of 2a to give azelaic and pelargonic acid is an established industrial process. [2] Am ultitude of methods have been reported to replace ozone with as afer oxidant. However,apractical alternative was only found about 10 years ago, [46] correlated with the development of catalytic methods for the oxidative cleavage with H 2 O 2 ,which has the potential for industrial application. [47] [48] [49] Behr et al. reported on the oxidative cleavage of 2b with H 2 O 2 (35 %, 8equiv.) catalyzed by ruthenium/dipicolinic acid (Scheme 9). [50] Atwostep process was industrialized by Matrica. [51] 2b is oxidized with H 2 O 2 ,c atalyzed by tungstic acid, to give vic-diol 30, which is cleaved with oxygen, catalyzed by cobalt acetate. [52] Thes elective hydrogenation of the complex mixture of natural polyunsaturated acids,s uch as 4a, 5a or the more complex 14 a and 15 a,t om onounsaturated fatty acids is acontinuing challenge. [53] Good results were obtained with Pd nanoparticles in polar organic solvents such as 1,2-propylenecarbonate [54] or PEG-4000 as complexing solvent. [55] A series of non-food oil derived methyl esters were selectively hydrogenated over Cu/SiO 2 . [56] All these selective hydrogenations occur with stereoisomerization of the cis-configured double bonds.S els et al. discussed the design of novel hydrogenation catalysts to enable the production of trans-free hydrogenated products for the food sector. [57] Thes ynthesis as well as properties and industrial applications of alkyl-branched fatty compounds have been reviewed. [58] Gooßen et al. used aRh/Pd catalyst to propenylate 4cgiving product 31 as amixture of isomers (Scheme 10). Pd catalyzes the conjugation of the two double bonds,which are propenylated with Rh catalysis. [59] Thep rotocol for the synthesis of well-defined alkyl-branched oleochemicals was considerably improved by using haloalkanes instead of chlorocarbonates [4] to give the hydroalkylation products in excellent to good yields (Scheme 11). [60] Importantly,t he reaction protocol was scalable (> 500 g 2b)a nd was also applied to substrates with two or more double bonds as well as to triglycerides. Theskeletal isomerization of unsaturated fatty acids such as 2a was performed in the presence of H + -ferrierite zeolite catalysts to give,a fter hydrogenation, methyl-branched isofatty acids with ar emarkable selectivity of up to about 80 % [61, 62] in contrast to the present industrial process. [58] Addition products of unsaturated fatty derivatives and maleic anhydride as well as various follow-up products are of interest because of their versatile properties in numerous applications. [63] Interestingly,the Rh-catalyzed reaction of 4a and maleic anhydride gave the cycloaddition products 33 a and 33 b in a1 :1 ratio (Scheme 12), [64] which are identical to the Diels-Alder addition products of 12 a and 13 a. [4] Compound 10 b,d erived from the seed oil of Sterculia foetida L,w as rearranged to the conjugated diene 34 with am ethylene branch as am ixture of two regioisomers with aselectivity of 99 %under Pd catalysis (Scheme 13). [65] 3.2.4. Hydroformylation [66] and Hydroaminomethylation [67] Thei somerizing hydroformylation [4, 68] of 2b was considerably improved using ap alladium isomerization and ar hodium hydroformylation catalyst simultaneously,affording the a,w-aldehyde ester. [69] Thec orresponding alcohol 35 was directly obtained using aRh/Ru/Ru ternary tandem catalytic system with Shvosh ydrogenation catalyst (Scheme 14). [70] Theimportant task of recycling the homogeneous hydroformylation rhodium catalyst has been addressed by organic solvent nanofiltration, [71] selective product crystallization, [72] and especially by thermomorphic solvent systems, [73] for example,acombination of water/1-butanol for the hydroformylation of 17 b [74] and 2b. [75] Most interesting are new developments in the reactor setup for gas-liquid-liquid multiphase catalysis,f or example,u sing aj et-loop reactor to improve the aqueous biphasic hydroformylation of 17 b and 2b. [76] Bis-hydroaminoalkylation of 17 b and 17 d with piperazine yielded long-chain linear diester 36 b and diol 36 d,r espectively,i nteresting substrates for polyesters (Scheme 15). Key to success was the selective crystallization of the product from the reaction mixture in > 98 %purity. [77] Themechanism of the isomerizing alkoxycarbonylation of unsaturated fatty compounds was studied in detail, including computational studies. [78] [79] [80] Mecking et al. fully analyzed the products of the methoxycarbonylation of 2b with the welldefined precatalyst [(dtbpx)Pd(OTf) 2 ], [81] and found the formation of the linear a,w-diester with as electivity of 90.6 %, besides all possible branched diesters in minor amounts. [82] Thed iester was obtained in high purity by simple recrystallization from methanol. Most importantly, the robust catalytic system is capable of transforming not only pure 2b,but also technical grade plant oils [83, 84] and microbial oils. [85] Thec atalyst can also be used for selective terminal carbonylation of the internal double bond of 2a with water as anucleophile to open adirect access to a,w-dicarboxylic acids such as 37 (Scheme 16). [86] Ther ecycling and reuse of the catalyst has been studied as well. [87, 88] Them etathesis reaction of unsaturated fatty compounds has been studied intensively over the past ten years and has been thoroughly reviewed. [89] [90] [91] [92] Studies have focused on the important topics self-metathesis and ethenolysis, [93] [94] [95] crossmetathesis with functionalized alkenes,a nd isomerizing metathesis. [96] 3.2.6.1. Self-Metathesis and Ethenolysis Self-metathesis of 2b gives the long-chain diester 38 and alkene 39 in only moderate yield in equilibrium, since olefin metathesis is ar eversible reaction (Scheme 17 a). However, self-metathesis of polyunsaturated fatty compounds,s uch as 5b,a llows full conversion to diester 38 and others,s ince volatile metathesis products,s uch as cyclohexa-1,4-diene or hex-3-ene,c an be easily removed in order to shift the equilibrium. [97] [98] [99] Self-metathesis has to be suppressed as far as possible in an ethenolysis reaction (Scheme 17 b). N-heterocyclic carbene (NHC) ruthenium catalysts,s uch as C1 (Scheme 18), provide selectivities as high as 95 %for the kinetic ethenolysis products 40 and 41,unfortunately with arelatively low TON of up to 5000 (Scheme 17 b). [100] It is well known that methylene-Ru intermediates,formed in the catalytic cycle of ethenolysis,a re less stable than alkylidene intermediates,t hus reducing the TONi nc omparison to that for alkenolysis with 1-alkenes and internal alkenes. [93] [94] [95] Hence,b utenolysis of 2b is performed industrially. [93c] To obtain an economically viable process,itwas stated that aT ON > 50 000 is required for the ethenolysis of 2b, based on the cost of the homogeneous catalyst. [93a] Them ost promising results have been obtained with Ru catalysts such as C2 and C3 bearing cyclic (amino)alkylcarbene (CAAC) ligands (Scheme 18). [101] TONs of 180 000 using 99.95 %pure ethene have been achieved at ac atalyst loading of 3ppm. These impressive results were obtained only when aglovebox was used. [102] Thee asily synthesized bis(CAAC)Ru catalyst C5 shows similar efficiencies, [103] and ad imeric indenylidene CAAC Ru complex C6 as well, though being more robust to standard-grade (99.9 %) ethene. [104] Grela et al. focused on practicability issues,such as reaction in air,ethene with 99.9 % purity,and undistilled 2bwith 90-95 %purity. [105] TheCAACbearing catalyst C4 was most efficient. Thes electivity was 95 %a nd the TONg oes up to 28 000. [106] 3.2.6.2. Cross-Metathesis with Functionalized Alkenes Cross-metathesis of unsaturated fatty compounds with functionalized alkenes,s uch as methyl acrylate, [107] dimethyl maleate, [108] maleic acid, [109] allyl acetate and cis-1,4-diacetoxy-2-butene, [110] [111] [112] acrylonitrile, [113, 114] or acrolein [115] gives straightforward access to interesting bifunctional unsaturated compounds with typically high (E)-stereoselectivity. In contrast, the cross-metathesis of 2a or 2d with (Z)-2butene-1,4-diol 42,u sing catalyst C7,y ielded (Z)-allyl alcohols 43 and 44 with high stereoselectivity ([Z]:[E] = 94:6) in 60-65 %y ield (Scheme 19). [116] 3. Thecooperative action of the Pd isomerization catalyst IC and the metathesis catalyst C8 (Scheme 18) enabled the transformation of unsaturated fatty compounds such as 2a or 2b into complex product blends having defined, tuneable properties,a ss hown by Gooßen et al. (Scheme 20) . [117] Alkenes and unsaturated mono-and diacids were obtained in adjustable distributions.T he method was also applied to improve rape seed oil biodiesel with ethene ( 1bar), in order to obtain boiling properties similar to conventional diesel fuel. [118] Biodiesel was also modified via self-and crossmetathesis with 1-hexene,r esulting in similarly improved boiling curves. [119] 4. Polymers 100 years after Staudingersf irst publication on polymerization, sustainability has become one of the most important topics for polymer scientists, [120] and of course for our society. Fatty acid derivatives have long been used for applications in polymer science; [4, 121, 122] detailed summaries with different foci are available. [10, [123] [124] [125] [126] [127] It is important to note that we had to be very selective in covering this flourishing and very large field of research in this brief overview,a nd thus,c omposites and blends,c ross-linked systems (i.e.t hermosets), copolymerization with other (renewable) monomers,o bviously unsustainable procedures,a sw ell as other directions could not be included or discussed in detail. Theu se of fatty acid based monomers for step-growth polymerization has significantly increased within the last 10 years and relates in large part to the efficient transformation of 2a, 5a,and 17 a as well as their derivatives to prepare AAas well as AB-type monomers (see also Section 3f or important synthesis routes). Ty pical AB-and AA-type monomers obtained from fatty acid derivatives that lead to linear, unbranched polyesters and polyamides are depicted in Scheme 21 and are predominantly derived via oxidative cleavage (Section 3.2.1), olefin metathesis (Section 3.2.6), isomerizing hydroformylation (Section 3.2.4), and thiol-ene addition. [128] An important advance is the development of long-chain polyesters from such starting materials that can mimic important properties of polyethylene,w hile offering degradability. [129, 130] Remarkably,p olyesters 19,19 and 23,23 were prepared on 100 gs cale;t he necessary dimethyl-1,19-nonadecanedioate monomer was directly prepared from technical-grade high oleic sunflower oil. Such polyesters offer suitable mechanical properties (elongation at break > 600 %; Youngsm odulus of 400 MPa) for non-wovens or extruded transparent films. [131] Similar long-chain polyesters can be obtained via different routes,f or instance from biotechnologically derived monomers [132, 133] or ring-opening polymerization of macrolactones. [134] Tw oh ighly remarkable monomers,t he very long-chain diesters 45 and 46,w ere prepared by Mecking et al. from 38 (Scheme 17) by isomerizing the central double bond selectively to the statistically disfavored a,b-position in acatalytic dynamic isomerizing crystallization approach. Subsequently, "chain doubling" was achieved by an additional cross-metathesis step to obtain ultra-long-chain a,w-difunctional building blocks of up to 48 carbons in length. [135] Polyester 48,48, derived from 46,s howed an unprecedentedly high melting point of 120 8 8C. Apart from polyesters,p olyurethanes,p olyamides,a nd polyacetals have been prepared from the monomers described in Scheme 21, of course after appropriate chemical modification. An ovel development in this context is the synthesis of polyethers via either catalytic reduction of the corresponding polyesters (Scheme 22 a), [28] or the catalytic reduction of the respective ester monomers and subsequent acyclicd iene metathesis (ADMET) or thiol-ene polymerization. [136] This route offers access to so far unknown longchain polyethers.C ompared to the respective polyesters,t he polyethers showed lower meting points,w hereby the difference in melting point decreased with increased spacing of the functional groups. [28] Ad etailed review on the manifold possibilities and advances offered by such different types of fatty acid derived polymer classes,f rom synthesis to properties and possible applications,isavailable. [137] Fatty acid based polyamides and polyurethanes were thoroughly reviewed recently,also addressing sustainability aspects. [138] Polyacetals should be specifically mentioned and can be obtained from medium-and long-chain fatty acid derived diols in an acidcatalyzed process with 1) an excess of diethoxymethane to yield the diacetals,which are polymerized after isolation and purification, [139] or 2) via direct polymerization of diols with an excess of diethoxymethane (Scheme 22 b). [140] This route has been termed acetal metathesis polymerization (AMP). ]139a] Studying the properties of the novel polyacetals revealed that the solid polymers display higher stability against hydrolytic degradation compared to their shorterchain counterparts. [140] Very recently,a ni mportant step towards practical application was demonstrated for long-chain polyethylenes such as polyester 18,18 as well as the polycarbonate 18 via closed loop chemical recycling. [141] Last but not least, it is worth mentioning af ew more selected examples of similar long-chain and linear polyesters, [142] polyamides, [143] polyethers, [136a] polycarbonates, [144] or Scheme 22. a) Polyethers obtained via catalyticr eduction of polyesters; [28] b) polyacetalso btained via so-called acetal metathesis polymerization (the example shown is from ref. [140] ). [139, 140] (non-isocyanate) polyurethanes [145] that can also be obtained via ADMET,t hiol-ene,o ro ther polymerization techniques. Step-Growth Reactions 4.1. Fatty acids offer the possibility to design branched monomers or hyperbranched polymers with interesting and unique properties.O ne such branched monomer precursor, which can be obtained via several catalytic and non-catalytic routes (see Section 3.2.1 for selected examples) is keto fatty acid ester 25 (Scheme 7), which is suitable for the synthesis of branched polyamides (after reductive amination of 25)w ith interesting properties,s uch as an increased hydrophobicity and improved elongation at break when copolymerized with Nylon 6.6. [34] Similar monomers can also be obtained via thiol-ene addition. [128f] Following the oxidation and amination route,m ethyl 10-aminoundecanoate and methyl 10-hydroxyundecanoate can be obtained from 17 b,r esulting in am ethyl-branched polyamide or polyester,r espectively. [146] In both cases,s teric hindrance resulted in more difficult polymerization and poorer thermal properties.Avery different route to polyesters with various degrees of branching was described using ADMET polymerization of linear and branched a,w-diene monomers (Scheme 23). [147] After hydrogenation, thermo-mechanical properties in accordance to some types of polyethylene were observed, offering asustainable alternative to olefin-based elastomers,e specially for specific applications requiring degradability.A typical monomers were obtained by forming ester enolates from saturated fatty acid methyl esters,which reacted with dimethyl carbonate to form malonates with different chain lengths (C 6 -C 16 ) and bearing saturated alkyl branches at C2 of the malonate. [148] Polyesters as well as polyamides were derived from these malonate monomers,a nd the thermal properties could be tuned owing to the direct correlation to the alkyl chain length. Ther oute via malonates was also adopted for the synthesis of fatty acid monomers bearing six-membered cyclic carbonates,w hich were used for the synthesis of nonisocyanate polyurethanes. [149] Moreover,branched polyacetals were prepared via the abovementioned acetal metathesis route (see Scheme 22) , in this case derived from heptanal and 17 a. [150] As pecial case of highly branched fatty acid derived monomers are the so-called dimer fatty acids (Scheme 24), classically obtained and industrially available since the 1950s via the intermolecular coupling of unsaturated fatty acids and their esters. [151] This process mainly proceeds via isomerization followed by aD iels-Alder reaction. Thei ndustrially obtained dimer acids are am ixture of several compounds (monomer,dimer,trimer,cyclic, aromatic structures), requiring extensive purification before polymerization. Such dimer acids generally provide high flexibility,p ronounced hydrophobicity,a nd hydrolysis stability,f or instance to polyurethanes. [152] Their use in polyamides,for example,ashot-melt adhesives or as reactive components,typically leads to lower crystallinity as well as lower melting temperatures. [153] Also applications in polyurethane foams, [154] coatings, [155] and controlled release materials [156] have been described. Over the years,a ss ummarized in ref. [157] ,a ttempts have been made to improve their synthesis.More recently,hydrobromination of oleic acid, followed by nucleophilic substitution with dithiols,resulted in new dimer structures. [158] Interestingly, 2b can be dimerized directly with ethane-1,2-dithiol in as imple UV-induced one-pot procedure to obtain the defined dimer acid 49 (Scheme 24) in one reaction step,w hich significantly reduces water uptake when used for polyamide synthesis. [157] Al arge variety of structurally defined dimer acids,s ome fully renewable (i.e. 50,S cheme 24), were prepared via catalytic Wacker-type oxidation of 2b, 6b,o r17 b,l eading to the respective keto fatty acid derivatives,w hich were subsequently dimerized via reductive amination. [159] When these compounds were copolymerized with 1,10-diaminodecane,h igh-molecular-weight polyamides with low glass transition and melting temperatures were obtained. Hyperbranched polymers derived from fatty acids are far less frequently described, yet offer interesting structures and properties.F or instance, 7b was transformed to an AB 2 monomer by thiol-ene addition of 2-mercaptoethanol in as olvent-free reaction. [160] Ther esulting hyperbranched polyesters showed lower complex viscosities than their linear analogues and low glass transition temperatures. Similarly, 17 b was used as as tarting material to obtain an AB 2 monomer by reaction with thioglycerol, [128e,161] resulting in hyperbranched polyesters with ahigh degree of branching and low inherent viscosity. [161] AB 2 and AB 3 monomers for Scheme 23. Branched polyesters, derived from castor and vernonia oil, mimicking the structure and properties of olefin-based elastomers. [147] Scheme 24. Industrially available (left) and new,m ore defined dimer fatty acid derivatives (right);p lease note that 49 and 50 are each mixtures of three regioisomers. hyperbranched polyesters were also prepared via epoxidation and ring opening of 2b, 6b, 7b,and 17 b. [162] Interestingly,the degree of branching depended on the type of monomer as well as on the conversion and the applied catalyst. Adifferent approach uses trifunctional (A 3 or B 3 )f atty acid derived monomers in combination with the respective B 2 or A 2 monomers in aD iels-Alder reaction between furans (A) and maleimides (B). [163] A 2 Ba nd AB 2 systems were also described. Most interestingly,t he Diels-Alder approach allowed for the thermoreversibility of the polymerization reaction. Highly branched polyesters could also be obtained by the so-called acyclict riene metathesis of high oleic sunflower oil [164] or the highly unsaturated Plukenetia conophora oil. [165] Theo ils could be polymerized directly under bulk conditions without any pretreatment. To obtain fully renewable monomers for chain-growth polymerization from fatty acid derivatives is more difficult than the approaches discussed in Section 4.1, and have thus been reported less frequently. As described in Section 3.2.6, 1,4-cyclohexadiene 51 can be obtained efficiently by self-metathesis of highly unsaturated plant oils or fatty acid methyl esters. [97, 98] Compound 51 was shown to be as uitable renewable platform molecule (Scheme 25) for the synthesis of poly(cyclohexadiene) via in situ isomerization and polymerization [166] as well as for the synthesis of polyamide 6 [167] and poly(caprolactone). [168] The latter two commercially important polymers could also be functionalized to tune their properties.1 ,4-Cyclohexadiene oxide was furthermore used as acomonomer for the synthesis of unsaturated polyesters as well as polycarbonates. [169] Ringopening polymerization (ROP) was also used for the solventfree copolymerization of methyl 9,10-epoxystearate with different cyclic anhydrides using a( salen)Cr III Cl catalyst and n-Bu 4 NCl as co-catalyst to yield polyesters with low glass transition temperatures. [170] Another interesting class of fatty acid based monomers for cationic ROP are 2-oxazolines, leading to materials suitable for the preparation of amphiphilic structures as well as for low-surface-energy and lowadhesive coatings. [171] Furthermore,avariety of monomers for radical polymerizations are described, leading to either cross-linked or copolymer systems that are outside the scope of this focused summary.Afew interesting new monomers and the corresponding fatty acid based homopolymers are worth mentioning. Most typically,p olymerizable moieties such as acrylates or methacrylates are attached to fatty alcohols or 7b, [172] leading to partially renewable monomers via often unbenign synthesis routes. [173] These monomers will not be discussed herein, as they were very recently reviewed. [172] Compounds 2a and 4a were transvinylated with vinyl acetate using 1mol %[ Ir(cod)Cl] 2 to yield fatty acid vinyl esters. [174] Subsequent free radical polymerization led to materials possibly useful as paints or varnishes via the oxidative drying of the unsaturation remaining in the side chains of the polymers.I nterestingly,t he even less activated olefinic double bond of 17 b could be directly copolymerized with vinyl acetate (up to 50 %) using apreformed alkylcobalt-(III) acetylacetonate (R-Co(acac) 2 )complex, where the alkyl group acts as ar adical initiator and the Co(acac) 2 as the controlling agent. [175] Molecular weights above 10 kDa could be achieved while maintaining relatively low dispersities. Furthermore,asustainable purification via supercritical CO 2 extraction was introduced, allowing the recovery of unreacted 17 b.F inally worth mentioning is ao ne-pot catalytic copolymerization of 2b or plant oils with ethylene using an isomerization catalyst and aB rookhart polymerization catalyst at the same time. [176] Theu se of isolated (immobilized) enzymes for the modification of fats,oils,and related lipids for oleochemistry is well documented in the literature. [4, 177] Biocatalysis using enzymes offers important advantages such as chemo-, regio-, and stereoselectivity under mild reaction conditions.Enzymes address some aspects of green chemistry,s ince they are biodegradable,u se mostly water as as olvent, and most importantly,t hey can catalyze ab road variety of reactions. Very recently,t wo reviews have been published on the industrial applications of biocatalysts. [178] Since the publication of our last review, [4] in addition to lipases,phospholipases (PLA) as well as afew other enzymes, such as P450-monooxygenases,h ave found their way into oleochemistry.L ipases have been widely applied for many decades to prepare structured triglycerides,m argarine,a nd biodiesel. Phospholipases,o nt he other hand, are the biocatalysts of choice for degumming.H ere,e specially the use of PLC was established [179] as an alternative to PLA 1 or PLA 2 . Examples of other enzymes are given in the subsequent sections.F or microbial biotransformations,s ubstantial progress in molecular biology and metabolic engineering allows the design of entirely new pathways in microorganisms.T his has opened new opportunities for lipid modification and enables the transformation of simple-often renewableprecursor molecules into valuable lipid-related products. [177b] Modern methods for enzyme discovery as well as advanced protein engineering tools have helped expand the biocatalytic toolbox and adjust enzymes for large-scale processing. [180] Scheme 25. 1,4-Cyclohexadiene 51 as arenewable platform chemical for the synthesis of various polymers. Furthermore,cascade reactions [181] open up new opportunities for the use of enzymes in oleochemistry. Ty pically,l ipases are used for the synthesis of esters (e.g. biodiesel production), as the presence of water will result in hydrolysis.A lthough it has been known for more than ad ecade that some lipases (or lipase-like enzymes) also have acyltransferase activity,o nly recently has substantial progress been reported. This includes lipase CAL-A and an enzyme from Candida parapsilosis (CpLIP2). Both enable the synthesis of esters,s uch as fatty acid ethyl esters (FAEE), in the presence of ab ulk aqueous phase.T hrough the use of rational protein design, the acyltransferase activity of lipase CAL-A could be substantially improved by as ingle point mutation (D122L) and up to 95 %F AEE could be produced from palm kernel oil in the presence of 5-10 %w ater in EtOH. [182] Thegroup led by Subileau and Dubreucq improved CpLIP2 and identified ab road range of further enzymes. [183] Very recently,t he structural and molecular reasons for this phenomenon were elucidated. [184] High acyltransferase activity correlates well with the hydrophobicity of the substratebinding pocket and ascoring system was proven to accurately predict the promiscuous acyltransferase activity from protein sequences in databases,w here more than at housand novel candidates were identified;s everal of them have been experimentally verified. [184, 185] Lipases have been successfully subjected to protein engineering in numerous reports. [180a] More recently,t he fatty acid selectivity of lipase CAL-A was improved to enable the enrichment of erucic acid 6a. [186] 6a is also present in Crambe abyssinica seed oil ( % 59 %) and its concentration needs to be elevated for oleochemical applications.Adetailed protein engineering study led to the identification of adouble mutant (V238L/V290L) with which the level of 6a could be increased to 74 %. [186b] Similarly,t he selectivity for gondoic acid 9a present in Camelina sativa oil was enhanced using CAL-A variants to enable its enrichment. [186a,c] Avery interesting enzyme class are the flavin-dependent hydratases,w hich add water to double bonds and thus form hydroxyl groups. [187] Mostly oleate hydratases have been studied, which convert oleic acid in ar egio-and stereoselective manner to the corresponding (R)-10-hydroxystearic acid (up to 100 gL À1 ). [188] OAshave also been included in cascade reactions to functionalize fatty acid derivatives,for instance to obtain long-chain aliphatic amines (see below). [189] In 2013, the first crystal structure of al inoleic acid hydratase was reported by the Feussner group, [190] followed by that of an oleate hydratase from Elizabethkingia meningoseptica. [191] Besides insights into the mechanism, this provided the basis for protein engineering to expand the substrate scope of OA, which can now catalyze the asymmetric hydration of terminal and internal alkenes (notably lacking acarboxylic group) also on preparative scale (up to 93 %c onversion, > 99 % ee, > 95 %regioselectivity). [192] Carboxylic acid reductases (CARs) are useful biocatalysts for the conversion of carboxylic acids into aldehydes under mild reaction conditions without overreduction to the corresponding alcohol. Aldehydes are especially important for the flavor and fragrance industry,a swell as for various other applications in chemistry as summarized in recent reviews, which also discuss the current status on the discovery, structures,a nd applications of CARs. [193] Fort heir catalytic activity,C ARs require coexpression of as uitable phosphopantetheinyl transferase (PPTase) and the cofactors NADPH and ATPinstoichiometric amounts.Thanks to the recent the elucidation of the first structures of the CARs from Nocardia iowensis and Segniliparus rugosus, [194] and to the recent development of ah igh-throughput assay,i mproved variants have already been generated by protein engineering. [195] Practically,often whole-cell systems are used and the cofactor ATPcan be readily recycled. On the other hand, the formed aldehydes are usually toxic to the host, e.g. E. coli. Thus, Tu rner and co-workers used isolated enzymes in ac ascade reaction (Scheme 26). [196] CARs have also been used for the reduction of dicarboxylic acids,y ielding diols such as 1,4-butanediol or 1,6hexanediol. [197] Carboxylic acids can also directly be converted into the corresponding carboxylic amides in the presence of ATPa nd an amine nucleophile,b ut NADPH must be excluded and thus only the adenylation domain of the CARi su sed in this case. [198] Ther ecycling of the expensive ATPf rom the formed AMP can be achieved in vitro with apolyphosphate kinase using cheap pyrophosphate (PPi). [199] This concept was first shown for SAM-dependent methyltransferases,n ow allowing larger scale applications of CARs. [200] Very interesting precursors for oleochemistry are,atleast in principle,a ccessible by decarboxylases,w hich can form terminal alkenes (with release of CO 2 ,S cheme 27) directly from fatty acids. [201] Three enzymatic systems have been studied in more detail:the fatty acid decarboxylase OleT,the medium-chain fatty acid decarboxylase UndA, and the decarboxylase UndB.A st he heme-dependent OleT requires electrons for in vitro applications,d ifferent strategies have been developed using the addition or in situ formation of H 2 O 2 ,c oupling with the CamA/CamB system to use NAD-(P)H or protein fusions,f or instance with ac atalase. [202] Obstacles to overcome remain the typically low yields due to the instability of these enzymes.F or OleT,t otal turnover numbers of > 2000 and product titers of up to 0.93 gL À1 have been reported. [203] TheK ourist group has furthermore demonstrated al ight-driven conversion of w-functionalized fatty acids using OleT in combination with aRu-based metathesis catalyst in as equential chemoenzymatic cascade in ab uffer/ isooctane system. [204] Combining several enzymes that catalyze different reactions in cascades enables am ore efficient access to complex products.I n2 013, ac ascade comprising an oleate hydratase, an alcohol dehydrogenase,aBaeyer-Villiger monoxygenase and finally an esterase was reported to yield w-hydroxy carboxylic acid or a,w-dicarboxylic acids directly from 2a. [205] This biocatalytic route is an alternative to the oleochemical processes,w here either pyrolysis or ozonolysis are traditionally applied. Such ac ascade was extended to make 11aminoundecanoic acid from 7a,leading to 77 %product from 300 mm 7a. [206] Thesynthesis of w-aminododecanoic acid from lauric acid on apilot scale was also reported using awhole-cell system for enzymatic oxidation and transamination. [207] Nowadays,c omplex products are produced in suitable microbial hosts that have been designed by metabolic engineering,for example,byintroducing artificial or improving existing pathways.T hus,b iofuels,f atty acid derivatives, and surfactants such as sophorolipids can be made directly in microorganisms.A sa ne xample,a ne ngineered pathway to produce the polyunsaturated fatty acid EPA( 15 a)-commonly obtained from fish oil-in the oleagineous yeast Yarrowia lipolytica was reported. [208] 15 a was formed in up to 15 %y east cell dry weight, whereby > 56 %o ft he total fatty acids was 15 a.T oachieve this titer,nine chimeric genes were newly introduced into the yeast;aD17-desaturase was shown to be the most important, besides am utation in the peroxisome. More recently,aRhodococcus opacus strain was engineered to produce free fatty acids (FFA) or FAEE and longchain hydrocarbons. [209] First, the formation of triglycerides from glucose was improved (82.9 gL À1 ). Next, an engineered strain with acyl-coenzyme As ynthetase genes deleted and overexpressing three lipases produced 50.2 gL À1 of FFAs. Another engineered strain, in which also heterologous aldehyde/alcohol dehydrogenase and wax ester synthase were overexpressed, made 50.2 gL À1 FAEEs.F inally,at hird construct enabled the formation of 5.2 gL À1 of hydrocarbons. All these values are substantially higher than those of previously reported E. coli-based systems. [210] Thus,metabolic engineering strategies can contribute to oleaginous biorefinery platforms for the sustainable production of chemicals and fuels. Selective oxidation of non-activated CÀHbonds is avery challenging reaction in organic synthesis,b ut it can be achieved efficiently using biocatalysis.T he oxidation of long-chain alkanes or fatty acids to a,w-diacids by Candida tropicalis,anatural degrader of these compounds,was initially already reported in the 1990ies. [133, 211] More recently,t he competing b-oxidation pathway in the strain C. tropicalis H5343 was targeted and after deletion of four genes,h igh yields of tetradecanedioic acid (54,2 10 gL À1 )f rom methyl myristate 52 were achieved (Scheme 28). [211] In another study,16genes involved in the oxidation of the w-hydroxy acids were deleted in the C. tropicalis DP428 strain. This led to the formation of 174 gL À1 of 14-hydroxytetradecanoic acid 53 by biotransformation of 52 (200 gL À1 ) within 148 h. [211] C. tropicalis is currently implemented on ac ommercial scale (40,000 tonnes per year). [212] These examples illustrate the high efficiency of P450s for the conversion of the native substrates in the native host. Microbial and plant oils are valuable and diverse feedstocks for industry. [213] To allow for an efficient and increasingly sustainable supply of fatty acids and thus to promote the above discussed possible applications,i mprovements in the production of fats and oils are of high importance.W hile oil production with crop plants on al arge scale is very well established, the use of microbial and algal fermentation is still restricted to high-value products in specialized organisms like Yarrowia, Mortierella, Chlorella,a nd Schizochytrium. [214] Until now,m ore than 450 different fatty acids of plant origin have been described (Scheme 1). During the last decade,t wo databases have been published summarizing data on the different fatty acids that can be found in plants and algae. [215, 216] Theb iosynthesis of oils and storage lipids in plants has been established over the last decades and this knowledge now serves as abasis for developing tailor-made oils with the help of modern biotechnology. [213, [217] [218] [219] Thep roduction may be optimized and/or manipulated in three steps ( Figure 3 ): 1) Oil biosynthesis,starting with fatty acid biosynthesis,which yields the backbone and chain lengths of up to 18 carbons. 2) Next, functional groups may be introduced, such as double bonds,h ydroxyl groups as in 7a,o rc yclopropane rings as in 10 a,orthe backbone can be further elongated up to C 36 . [213, 220] 3) Finally,t hese fatty acids need to be transferred into triacylglycerols (TAG)o rw ax esters (WE) by specific acyltransferases. [221] Scheme 28. Conversion of methyl myristate 52 to the corresponding w-hydroxyacid 53 or a,w-diacid 54 by Candida tropicalis using P450s, oxidases, and alcohol dehydrogenases (ADHs). [211] Angewandte Chemie Reviews 6.1. Improving Existing Oil Qualities in Crop Plants While classical breeding aims at improving the yield and composition of existing plant oils,m odern biotechnological methods can transfer foreign genes to crop plants to improve the yield and/or to generate new oil qualities even beyond natural limits. [217] Over the last decade,t he "push/pull concept" has been developed to increase oil yield in crop plants. [222] Here,f atty acid biosynthesis is increased by overexpressing the transcription factor WRINKLED1 (WRI1), which "pushes" additional substrate into the pathway.T his is combined by expressing the final enzyme ACYL-COA:D-IACYLGLYCEROL ACYLTRANSFERASE 1(DGAT1) of the oil-forming pathway,w hich "pulls" fatty acids out of the membranes into the storage lipid pool. So far, the overexpression of WRI1 alone in soybean led to an increase of up to 3% in the oil content under field conditions. [223] In corn, an atural mutation leading to an amino acid exchange in DGAT1 resulted in an increase in oil and 2acontents by up to 41 %a nd 107 %, respectively. [224] Besides increasing the general flux into the oil, the assembly of the triacylglycerol molecules can also often limit the yield. In the case of the high production of erucic acid (6a)i nr apeseed, an atural limit is about 50 % 6a,b ecause in many commercial varieties as pecific acyl transferase is missing, which transfers 6a into the sn2-position of the triglyceride.T his limitation was overcome by overexpressing the endogenous rapeseed FATTY ACID ELONGASE 1( FAE1, "push" approach) in combination with an ACYL-COA:LYSOPHOSPHATIDIC ACID ACYLTRANSFERASE (LPAAT, "pull" approach) gene from Limnanthes douglasii that had ah igh substrate preference for 6a.I ndeed, the obtained rapeseed oil from these plants contained up to 72 %of6a. [225] Another approach to produce 6a is to establish alternative industrial oil crops like Crambe abyssinica that already have higher endogenous amounts of this fatty acid in their seed oil. This led to the production of 77 %of6a. [226] Over the last decade,i mportant achievements have been made to generate new oil qualities in existing crop plants.The prerequisites for the production of 7a in rapeseed are currently analyzed by transferring all necessary genes,s tep by step,i nto the model brassicaceae Arabidopsis thaliana (thale cress). Thee xpression of the FATTY ACID HYDROXYLASE12 (FAH12) gene from castor bean alone led to adrastic reduction of the oil content and accumulation of 7a was limited to about 13 %i nA. thaliana. [227] However, the additional expression of three acyltransferase genes, which specifically incorporate 7a at each stereochemical position of the TAGm olecule,r esulted in normal oil accumulation, which now contained up to 44 %o f7a. [228] Thep roduction of the cyclopropane fatty acid dihydrosterculic acid 11 a was recently established in the biofuel crop Camelina sativa (false flax). [229] [230] [231] Here,e xpression of an enzyme from E. coli resulted in an accumulation of about 10 %o f11 a in the seed oil of an high oleic acid line. [232] An additional increase to more than 15 %w as achieved by introducing aL PA AT gene from Sterculia foetida (skunk tree). Thef ormation of the conjugated fatty acids a-eleostearic acid 13 a and punicic acid 14 a in soybean, tobacco,and rapeseed by introducing the corresponding conjugases alone is currently limited to about 15 %. [233] [234] [235] In summary,t he picture emerges that the introduction of only one single enzyme catalyzing the formation of anew fatty acid results in the accumulation at levels between 10 and 15 %incrop plants. In many cases,this is due to alimited transfer of the fatty acid from the membrane lipid pool to the storage lipid pool. [217, 221, 236] Future work is therefore needed to identify the necessary acyltransferases. [237] While the oil qualities discussed above are primarily used as feedstock for the chemical industry,the production of very long chain w3-fatty acids in crop plants is for feed and food purposes.Here,b etween three and seven foreign genes have to be transferred into crop plants. [218, 238 ] Similar to the production of 7aand 11 a discussed above,their yield depends not only on their effective biosynthesis and transfer into the storage lipid fraction (steps 2a nd 3i nF igure 3), but also on the oil composition of the crop plant that is used as the production platform. While the minimal set of three genes needed for the production of eicosapentaenoic acid 15 a led to the formation of about 1% in linseed, because this plant oil is already rich in the w3-fatty acid 5a (about 50 %) as starting material, the same construct led only to the formation of half of the amount in rapeseed. [239, 240] Consequently another crop plant rich in 5a, C. sativa,iscurrently used as the platform for the production of 15 a and docosahexaenoic acid 16 a.Inorder to further optimize this oil as astarting material, its DGAT1 gene,which confers the transfer of saturated and monounsaturated fatty acids into the seed oil, was downregulated leading to an increase in a-linolenic acid to about 56 %. [241] In an independent approach, all three FAE1 genes that are responsible for chain elongation longer than C18 were mutagenized, resulting in a a-linolenic acid content of about 50 %. [242] Recently, C. sativa plants transformed with asevengene construct were shown to produce about 10 %ofeach 15 a Reviews and 16 a in field trials. [243] This oil composition mirrors closely the quality of fish oil. Through the use of another combination of seven genes,also about 10 %of16 a was produced in field trails in rapeseed. [244] In the case of this trial, it should be noted that similar approaches were used to optimize the production of 15 a and 16 a in the marine diatom Phaeodactylum tricornutum. [245] To produce biofuels,l ubricants,o ro ther industrial feedstocks from plant oils,often only the fatty acids are used and the remaining glycerol might be aleftover. In order to address this problem, two different oil qualities are under development. Aspecific DGATenzyme introduces an acetate group to the sn3-position of TAGm olecules to yield so-called acetyl-TAG species.T his oil quality has the advantage that it can be used directly as af uel or lubricant. Introducing an enzyme from Euonymus alatus (burning bush) into Camelina yielded about 70 %t he corresponding acetyl-TAGsi nt he seed oil in field trials. [246] Introducing the same enzyme into Camelina lines producing high amounts of medium-chain fatty acids (C 8 -C 14 )i nt heir seed oil even improved the properties of the oil. [247] Thes econd strategy aims to replace TAGmolecules by wax ester (WE) molecules in the seed oil of crop plants.Here,afatty acid is directly esterified to afatty alcohol by aw ax synthase.T his acyltransferase and af atty acid reductase are introduced, the latter providing the enzyme with fatty alcohols. [248, 249] So far,b etween 30 and 50 %o ft he TAGi nt he seed oil was replaced by WE. Ther esulting oil quality ranged from wax esters derived from 6a and 6c in Crambe abyssinica and 2a and 2d to even shorter chain lengths in Camelina,d epending on the corresponding fatty acid pattern of the genetic background used. [250] [251] [252] Although the yield of oilseed crops has increased over the last decades,itisstill achallenge to meet the steadily growing demand for plant oils as renewable resources or for highenergy feed and food applications (compare also Section 2). [217, 231, 236, 249, 253] One strategy to solve this problem may be the production of oil in all vegetative tissues instead of seeds only.T his can be achieved by driving the expression of the whole oil biosynthesis machinery under the control of senescence-specific promotors at the end of ap lantsa nnual life cycle,w hen its biomass has reached its maximum ( Figure 3 ). Theo ilseed crop plant tobacco serves as am odel to develop strategies to reach this goal and the "push and pull" concept was further extended to "push, pull, and protect". [236, 254] Thel atter point addresses appropriate packaging and unwanted degradation of the product in the cells of the sink tissue.M ore than 15 %o fTAGa ccumulated in tobacco leaves by the co-expression of three genes:W RI1, DGAT1, and oleosin ("protect"). [255] By additional silencing of the TAGd egrading lipase SDP1, accumulation could be increased up to 33 %i nt obacco and up to 8.4 %i ns orghum leaves. [256, 257] Again similar approaches were used to optimize oil production in the marine diatom Phaeodactylum tricornutum,inthe heterokont oleaginous microalga Nannochloropsis oceanica,a nd in the oleaginous fungus Mortierella alpina. [258] [259] [260] [261] Oils and fats of vegetable and animal origin have been and probably will remain the most important renewable feedstock of the chemical industry.Itcan be expected that the observed geographical shift of oleochemical production to South East Asia will continue during the next decade.Selective catalytic reactions across the double bond has made important advances.T he catalytic oxidative cleavage of the C-C double bond as well as the butenolysis of 2b has been industrialized. It may be assumed that more reactions will be commercialized, for example ethenolysis and isomerizing alkoxycarbonylation. C-H activation of the saturated alkyl chain has not been tackled in this review and should be more intensively addressed in the coming decade.M icrobial oils have been used increasingly as substrates for catalytic transformations.M ore examples will be applied specifically to these substrates that are becoming more readily available. Then ew fatty acid derivatives discussed are important as substrates for the synthesis,a nd, hopefully,p roduction of ag reat variety of polyesters,p olyamides,a nd polyurethanes. Equally importantly,e nzyme or whole-cell catalysis for the modification of fats and oils as well as the de novo synthesis of various fatty acids from abundantly available renewable crop plants will contribute to further advancing the field. Angew.C hem. Int OECD-FAO Agricultural Outlook ;b )Oilseeds:W orld Markets and Tr ade,U SDA, September 2020 Angew.C hem. Int Angew.C hem. Int Fett Wiss.T echnol Wiley &Sons,Hoboken Angew.C hem. Int ;b )A.G andini, T. M. Lacerda,i nPolymers from Plant Oils Angew.C hem. Int 220, 1800440;b )M.F irdaus,M .A.R.M eier Cramail 85 -103;b ) Lipid modification by enzymesa nd engineered microbes Angew.C hem. 2021, 133,8 9-123;b )B .H auer, ACSC atal Oil Mill Gazet ProcessB iochem i nLipid Modification by Enzymes and Engineered Microbes Andexer, Angew.C hem. Int Lipid modification by enzymes and engineered microbes Proc.N atl. Acad. Sci Microbial Lipid Production:Methods and Protocols TheA merican Society of Plant Biologists,Rockville,M D Proc. Nutr.S oc Proceedings-The 12th International Rapeseed Congress Sustainable Development in Cruciferous Oilseed Crops Production Perspectives on new crops and new uses Version of record online Thea uthors are grateful for financial support from the Deutsche Forschungsgemeinschaft (DFG), Bundesministerium fürB ildung und Forschung (BMBF), Bundesministerium fürE rnährung und Landwirtschaft (BMEL), the European Union, and the Fonds der Chemischen Industrie (FCI). Open access funding enabled and organized by Projekt DEAL. Theauthors declare no conflict of interest.