生物转化脂肪酸合成ω-羟基酸和ω-氨基酸研究进展

doi:10.11949/0438-1157.20200438

摘要/Abstract

摘要：

ω-羟基脂肪酸和ω-氨基脂肪酸可广泛用于聚酯、聚酰胺等高分子的合成以及润滑油、生物燃料、医药中间体等化工产品的生产。近年来，以自然界丰富的可再生资源脂肪酸为绿色原料，生产这类可降解的生物基材料及化学品引起了人们的广泛兴趣，其中从植物油中的油酸、亚油酸等脂肪酸出发生产中链脂肪酸及其羟基、氨基衍生物的非天然生物催化反应也越来越丰富，是合成生物学技术在油脂资源转化方面的一个重要应用。综述了近年来中链ω-羟基脂肪酸与ω-氨基脂肪酸生物合成的研究进展，展示了通过多酶级联催化反应将可再生的脂肪酸生物转化，可持续生产9-羟基壬酸、6-氨基己酸、ω-氨基十二烷酸等高附加值精细化学品的合成路径和应用前景。

关键词: ω-氨基脂肪酸, 生化工程, 多酶级联反应, 催化剂, 酶, ω-羟基脂肪酸, 植物油

Abstract:

ω-Hydroxy fatty acids and ω-amino fatty acids can be widely used in the synthesis of polymers such as polyester and polyamide, as well as the production of chemical products such as lubricants, biofuels, and pharmaceutical intermediates. Using of the most abundant natural fatty acids as raw materials to produce fatty acid derivatives has caused extensive researches. In recent years, the biosynthetic reactions for producing medium-chain fatty acid derivatives have become more abundant. This article reviews the research progress in biosynthesis of mid-chain ω-hydroxy fatty acids and ω-amino fatty acids in recent years, indicating the synthetic routes and application potential for the sustainable production of value-added fine chemicals such as 9-hydroxynonanoic acid, 6-aminocaproic acid, and ω-aminododecanoic acid using multi-enzyme cascades.

Key words: ω-amino fatty acids, biochemical engineering, cascade multi-enzymatic reactions, catalyst, enzyme, ω-hydroxy fatty acids, plant oil

中图分类号:

Q 814.9

丁良怡, 种刚刚, 潘江, 许建和. 生物转化脂肪酸合成ω-羟基酸和ω-氨基酸研究进展[J]. 化工学报, 2020, 71(9): 3919-3932.

Liangyi DING, Ganggang CHONG, Jiang PAN, Jianhe XU. Advances in biosynthesis of fatty acids to ω-hydroxyacids and ω-amino acids[J]. CIESC Journal, 2020, 71(9): 3919-3932.

图/表 4

参考文献 74

1	Biermann U, Friedt W, Lang S, et al. New syntheses with oils and fats as renewable raw materials for the chemical industry[J]. Angew. Chem. Int. Ed., 2000, 39(13): 2206-2224.
2	Biermann U, Bornscheuer U, Meier M A, et al. Oils and fats as renewable raw materials in chemistry[J]. Angew. Chem. Int. Ed., 2011, 50(17): 3854-3871.
3	Seo J H, Lee S M, Lee J, et al. Adding value to plant oils and fatty acids: biological transformation of fatty acids into α-hydroxycarboxylic, α,ω-dicarboxylic, and ω-aminocarboxylic acids[J]. J. Biotechnol., 2015, 216: 158-166.
4	Metzger J O, Bornscheuer U. Lipids as renewable resources: current state of chemical and biotechnological conversion and diversification[J]. Appl. Microbiol. Biotechnol., 2006, 71(1): 13-22.
5	Köckritz A, Martin A. Synthesis of azelaic acid from vegetable oil-based feedstocks[J]. Eur. J. Lipid Sci. Technol., 2011, 113(1): 83-91.
6	Scrimgeour C. Chemistry of fatty acids[M]//Shahidi F. Bailey􀆳s Industrial Oil and Fat Products. 6th ed. Scotland: John Wiley & Sons, Inc., 2005: 1-43.
7	Rus A Z. Polymers from renewable materials[J]. Sci. Prog., 2010, 93(3): 285-300.
8	Chung H, Yang J E, Ha J Y, et al. Bio-based production of monomers and polymers by metabolically engineered microorganisms[J]. Curr. Opin. Biotechnol., 2015, 36: 73-84.
9	Richter M, Boldescu V, Graf D, et al. Synthesis, biological evaluation, and molecular docking of combretastatin and colchicine derivatives and their hCE1-activated prodrugs as antiviral agents[J]. ChemMedChem, 2019, 14(4): 469-483.
10	Cao Y, Zhang X. Production of long-chain hydroxy fatty acids by microbial conversion[J]. Appl. Microbiol. Biotechnol., 2013, 97(8): 3323-3331.
11	Hou C. Production of hydroxy fatty acids by biocatalysis[M]//Knothe J, Derksen J T P. Recent Developments in the Synthesis of Fatty Acid Derivatives. Champaign, Illinois: AOCS Press, 1999: 213-226.
12	Kim S K, Park Y C. Biosynthesis of ω-hydroxy fatty acids and related chemicals from natural fatty acids by recombinant Escherichia coli[J]. Appl. Microbiol. Biotechnol., 2019, 103(1): 191-199.
13	Otte K B, Kirtz M, Nestl B M, et al. Synthesis of 9-oxononanoic acid, a precursor for biopolymers[J]. ChemSusChem, 2013, 6(11): 2149-2156.
14	Song J W, Jeon E Y, Song D H, et al. Multistep enzymatic synthesis of long-chain α,ω-dicarboxylic and ω-hydroxycarboxylic acids from renewable fatty acids and plant oils[J]. Angew. Chem. Int. Ed., 2013, 52(9): 2534-2537.
15	Koppireddi S, Seo J H, Jeon E Y, et al. Combined biocatalytic and chemical transformations of oleic acid to ω-hydroxynonanoic acid and α,ω-nonanedioic acid[J]. Adv. Synth. Catal., 2016, 358(19): 3084-3092.
16	Jeon E Y, Seo J H, Kang W R, et al. Simultaneous enzyme/whole-cell biotransformation of plant oils into C₉ carboxylic acids[J]. ACS Catal., 2016, 6(11): 7547-7553.
17	Seo E J, Yeon Y J, Seo J H, et al. Enzyme/whole-cell biotransformation of plant oils, yeast derived oils, and microalgae fatty acid methyl esters into n-nonanoic acid, 9-hydroxynonanoic acid, and 1,9-nonanedioic acid[J]. Bioresour. Technol., 2018, 251: 288-294.
18	Jang H Y, Jeon E Y, Baek A H, et al. Production of ω-hydroxyundec-9-enoic acid and n-heptanoic acid from ricinoleic acid by recombinant Escherichia coli-based biocatalyst[J]. Process Biochem., 2014, 49(4): 617-622.
19	Cho Y H, Kim S J, Kim J Y, et al. Effect of PelB signal sequences on Pfe1 expression and ω-hydroxyundec-9-enoic acid biotransformation in recombinant Escherichia coli[J]. Appl. Microbiol. Biotechnol., 2018, 102(17): 7407-7416.
20	Qi Y K, Zheng Y C, Zhang Z J, et al. Efficient transformation of linoleic acid into 13(S)-hydroxy-9,11-(Z,E)-octadecadienoic acid using putative lipoxygenases from cyanobacteria[J]. ACS Sustainable Chem. Eng., 2020, 8: 5558-5565.
21	Gonzalo G, Mihovilovic M, Fraaije M. Recent developments in the application of Baeyer-Villiger monooxygenases as biocatalysts[J]. ChemBioChem: Eur. J. Chem. Biol., 2010, 11: 2208-2231.
22	Rehdorf J, Kirschner A, Cloning Bornscheuer U., expression and characterization of a Baeyer-Villiger monooxygenase from Pseudomonas putida KT2440[J]. Biotechnol. Lett.,2007, 29(9): 1393-1398.
23	Kirschner A, Altenbuchner J, Bornscheuer U T. Cloning, expression, and characterization of a Baeyer-Villiger monooxygenase from Pseudomonas fluorescens DSM 50106 in E. coli[J]. Appl. Microbiol. Biotechnol., 2007, 73(5): 1065-1072.
24	Yu J M, Liu Y Y, Zheng Y C, et al. Direct access to medium-chain α,ω-dicarboxylic acids by using a Baeyer-Villiger monooxygenase of abnormal regioselectivity[J]. ChemBioChem, 2018, 19(19): 2049-2054.
25	Jang H Y, Singha K, Kim H H, et al. Chemo-enzymatic synthesis of 11-hydroxyundecanoic acid and 1,11-undecanedioic acid from ricinoleic acid[J]. Green Chem., 2016, 18(4): 1089-1095.
26	Seo J H, Kim H H, Jeon E Y, et al. Engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalyst for large scale biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid[J]. Sci. Rep., 2016, 6: 28223.
27	Song J W, Lee J H, Bornscheuer U T, et al. Microbial synthesis of medium-chain α,ω-dicarboxylic acids and ω-aminocarboxylic acids from renewable long-chain fatty acids[J]. Adv. Synth. Catal., 2014, 356(8): 1782-1788.
28	Dirusso C C, Black P N. Bacterial long chain fatty acid transport: gateway to a fatty acid-responsive signaling system[J]. J. Biol. Chem., 2004, 279(48): 49563-49566.
29	Singh P, Sharma L, Kulothungan S R, et al. Effect of signal peptide on stability and folding of Escherichia coli thioredoxin[J]. PLoS One, 2013, 8(5): e63442.
30	Desbois A P, Smith V J. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential[J]. Appl. Microbiol. Biotechnol., 2010, 85(6): 1629-1642.
31	Woo J M, Kim J W, Song J W, et al. Activation of the glutamic acid-dependent acid resistance system in Escherichia coli BL21(DE3) leads to increase of the fatty acid biotransformation activity[J]. PLoS One, 2016, 11(9): e0163265.
32	Schrewe M, Julsing M K, Lange K, et al. Reaction and catalyst engineering to exploit kinetically controlled whole-cell multistep biocatalysis for terminal FAME oxyfunctionalization[J]. Biotechnol. Bioeng., 2014, 111(9): 1820-1830.
33	Hilker I, Gutiérrez M C, Furstoss R, et al. Preparative scale Baeyer-Villiger biooxidation at high concentration using recombinant Escherichia coli and in situ substrate feeding and product removal process[J]. Nat. Protocols, 2008, 3(3): 546-554.
34	Dirusso C C, Black P N. Long-chain fatty acid transport in bacteria and yeast. Paradigms for defining the mechanism underlying this protein-mediated process[J]. Mol. Cell. Biochem., 1999, 192(1): 41-52.
35	Jeon E Y, Song J W, Cha H J, et al. Intracellular transformation rates of fatty acids are influenced by expression of the fatty acid transporter FadL in Escherichia coli cell membrane[J]. J. Biotechnol., 2018, 281: 161-167.
36	Shin J, Yu J, Park M, et al. Endocytosing Escherichia coli as a whole-cell biocatalyst of fatty acids[J]. ACS Synth. Biol., 2019, 8(5): 1055-1066.
37	Seo E J, Kang C W, Woo J M, et al. Multi-level engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalysts for the production of C₉ chemicals from oleic acid[J]. Metab. Eng., 2019, 54: 137-144.
38	Woo J M, Jeon E Y, Seo E J, et al. Improving catalytic activity of the Baeyer-Villiger monooxygenase-based Escherichia coli biocatalysts for the overproduction of (Z)-11-(heptanoyloxy)undec-9-enoic acid from ricinoleic acid[J]. Sci. Rep., 2018, 8(1): 10280-10290.
39	崔书健. 了不起的尼龙家族[J]. 纺织科学研究, 2019, 170(2): 68-70.
	Cui S J. Great nylon family[J]. Text. Sci. Res., 2019, 170(2): 68-70.
40	李玉红. 维生素B12口服制剂的改进配方及用途: 102526088A[P]. 2012-07-04.
	Li Y H. Improved formula of vitamin B12 oral preparation and application: 102526088A[P]. 2012-07-04.
41	赢创工业集团股份有限公司. ω-氨基脂肪酸的生产: 103881933A[P]. 2014-06-25.
	Evonik Industries Ag. Production of omega-amino fatty acids: 103881933A[P]. 2014-06-25.
42	阿肯马法国公司. ω-氨基链烷酸的合成方法: 101663264A[P]. 2010-03-03.
	France Arkema. Method for the synthesis of omega-amino-alkanoic acids: 101663264A[P]. 2010-03-03.
43	Stadler B M, Wulf C, Werner T, et al. Catalytic approaches to monomers for polymers based on renewables[J]. ACS Catal., 2019, 9(9): 8012-8067.
44	Hayes K S. Industrial processes for manufacturing amines[J]. Appl. Catal. A: General, 2001, 221(1): 187-195.
45	Groger H. Biocatalytic concepts for synthesizing amine bulk chemicals: recent approaches towards linear and cyclic aliphatic primary amines and ω-substituted derivatives thereof[J]. Appl. Microbiol. Biotechnol., 2019, 103(1): 83-95.
46	France Arkema. Method for synthesising omega-amino-alkanoic acids or the esters thereof from natural fatty acids: WO2010004219A2[P]. 2010-01-14.
47	Louis K, Beauchene E, Vivier L, et al. Reductive amination of aldehyde ester from vegetable oils to produce amino ester in the presence of anhydrous ammonia[J]. Chemistry Select, 2016, 1(9): 2004-2008.
48	Ahsan M M, Jeon H, Nadarajan S P, et al. Biosynthesis of the nylon 12 monomer, ω-aminododecanoic acid with novel CYP153A, AlkJ, and ω-TA enzymes[J]. Biotechnol. J., 2018, 13(4): e1700562.
49	Sattler J H, Fuchs M, Mutti F G, et al. Introducing an in situ capping strategy in systems biocatalysis to access 6-aminohexanoic acid[J]. Angew. Chem. Int. Ed., 2014, 53(51): 14153-14157.
50	Bowen C H, Bonin J, Kogler A, et al. Engineering Escherichia coli for conversion of glucose to medium-chain ω-hydroxy fatty acids and α,ω-dicarboxylic acids[J]. ACS Synth. Biol., 2016, 5(3): 200-206.
51	Lee D S, Song J W, Voß M, et al. Enzyme cascade reactions for the biosynthesis of long chain aliphatic amines from renewable fatty acids[J]. Adv. Synth. Catal., 2019, 361(6): 1359-1367.
52	Sung S, Jeon H, Sarak S, et al. Parallel anti-sense two-step cascade for alcohol amination leading to ω-amino fatty acids and α,ω-diamines[J]. Green Chem., 2018, 20(20): 4591-4595.
53	Schrewe M, Ladkau N, Bühler B, et al. Direct terminal alkylamino-functionalization via multistep biocatalysis in one recombinant whole-cell catalyst[J]. Adv. Synth. Catal., 2013, 355(9): 1693-1697.
54	Ladkau N, Assmann M, Schrewe M, et al. Efficient production of the nylon 12 monomer ω-aminododecanoic acid methyl ester from renewable dodecanoic acid methyl ester with engineered Escherichia coli[J]. Metab. Eng., 2016, 36: 1-9.
55	Ahsan M, Patil M, Jeon H, et al. Biosynthesis of nylon 12 monomer, ω-aminododecanoic acid using artificial self-sufficient P450, AlkJ and ω-TA[J]. Catalysts, 2018, 8(9): 400.
56	Simon R C, Richter N, Busto E, et al. Recent developments of cascade reactions involving ω-transaminases[J]. ACS Catal., 2013, 4(1): 129-143.
57	Scheps D, Malca S H, Hoffmann H, et al. Regioselective ω-hydroxylation of medium-chain n-alkanes and primary alcohols by CYP153 enzymes from Mycobacterium marinum and Polaromonas sp. strain JS666[J]. Org. Biomol. Chem., 2011, 9(19): 6727-6733.
58	Maier T, Förster H H, Asperger O, et al. Molecular characterization of the 56-kDa CYP153 from Acinetobacter sp.EB104[J]. Biochem. Biophys. Res. Commun., 2001, 286(3): 652-658.
59	van Beilen J B, Wubbolts M G, Witholt B. Genetics of alkane oxidation by Pseudomonas oleovorans[J]. Biodegradation, 1994, 5(3/4): 161-174.
60	Schrewe M, Magnusson A, Willrodt C, et al. Kinetic analysis of terminal and unactivated C—H bond oxyfunctionalization in fatty acid methyl esters by monooxygenase-based whole-cell biocatalysis[J]. Adv. Synth. Catal., 2011, 353(18): 3485-3495.
61	Kirmair L, Skerra A. Biochemical analysis of recombinant AlkJ from Pseudomonas putida reveals a membrane-associated, flavin adenine dinucleotide-dependent dehydrogenase suitable for the biosynthetic production of aliphatic aldehydes[J]. Appl. Environ. Microbiol., 2014, 80(8): 2468-2477.
62	Taylor P P, Pantaleone D P, Senkpeil R F. Novel biosynthetic approaches to the production of unnatural amino acids using transaminases[J]. Trends Biotechnol., 1998, 16(10): 412-418.
63	Slabu I, Galman J L, Lloyd R C, et al. Discovery, engineering, and synthetic application of transaminase biocatalysts[J]. ACS Catal., 2017, 7(12): 8263-8284.
64	Höhne M, Bornscheuer U T. Biocatalytic routes to optically active amines[J]. ChemCatChem, 2009, 1(1): 42-51.
65	Richter N, Farnberger J E, Pressnitz D, et al. A system for ω-transaminase mediated (R)-amination using L-alanine as an amine donor[J]. Green Chem., 2015, 17(5): 2952-2958.
66	Tseliou V, Knaus T, Masman M F, et al. Generation of amine dehydrogenases with increased catalytic performance and substrate scope from ε-deaminating L-lysine dehydrogenase[J]. Nat. Commun., 2019, 10(1): 3717.
67	Citoler J, Derrington S R, Galman J L, et al. A biocatalytic cascade for the conversion of fatty acids to fatty amines[J]. Green Chem., 2019, 21(18): 4932-4935.
68	Martínez A T, Ruiz-Dueñas F J, Camarero S, et al. Oxidoreductases on their way to industrial biotransformations[J]. Biotechnol. Adv., 2017, 35(6): 815-831.
69	Carro J, González-Benjumea A, Fernández-Fueyo E, et al. Modulating fatty acid epoxidation vs hydroxylation in a fungal peroxygenase[J]. ACS Catal., 2019, 9(7): 6234-6242.
70	Ricca E, Brucher B, Schrittwieser J H. Multi-enzymatic cascade reactions: overview and perspectives[J]. Adv. Synth. Catal., 2011, 353(13): 2239-2262.
71	Mutti F G, Knaus T, Scrutton N S, et al. Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades[J]. Science, 2016, 47(6): 1525-1529.
72	Schrittwieser J H, Velikogne S, Hall M, et al. Artificial biocatalytic linear cascades for preparation of organic molecules[J]. Chem. Rev., 2018, 118(1): 270-348.
73	Liu S, Zhang X, Liu F, et al. Designing of a cofactor self-sufficient whole-cell biocatalyst system for production of 1,2-amino alcohols from epoxides[J]. ACS Synth. Biol., 2019, 8(4): 734-743.
74	Song J W, Seo J H, Oh D K, et al. Design and engineering of whole-cell biocatalytic cascades for the valorization of fatty acids[J]. Catal. Sci. Technol., 2020, 10(1): 46-64.

[1]	陈杰, 林永胜, 肖恺, 杨臣, 邱挺. 胆碱基碱性离子液体催化合成仲丁醇性能研究[J]. 化工学报, 2023, 74(9): 3716-3730.
[2]	杨学金, 杨金涛, 宁平, 王访, 宋晓双, 贾丽娟, 冯嘉予. 剧毒气体PH₃的干法净化技术研究进展[J]. 化工学报, 2023, 74(9): 3742-3755.
[3]	李艺彤, 郭航, 陈浩, 叶芳. 催化剂非均匀分布的质子交换膜燃料电池操作条件研究[J]. 化工学报, 2023, 74(9): 3831-3840.
[4]	孟令玎, 崇汝青, 孙菲雪, 孟子晖, 刘文芳. 改性聚乙烯膜和氧化硅固定化碳酸酐酶[J]. 化工学报, 2023, 74(8): 3472-3484.
[5]	杨欣, 彭啸, 薛凯茹, 苏梦威, 吴燕. 分子印迹-TiO₂光电催化降解增溶PHE废水性能研究[J]. 化工学报, 2023, 74(8): 3564-3571.
[6]	杨菲菲, 赵世熙, 周维, 倪中海. Sn掺杂的In₂O₃催化CO₂选择性加氢制甲醇[J]. 化工学报, 2023, 74(8): 3366-3374.
[7]	李凯旋, 谭伟, 张曼玉, 徐志豪, 王旭裕, 纪红兵. 富含零价钴活性位点的钴氮碳/活性炭设计及甲醛催化氧化应用研究[J]. 化工学报, 2023, 74(8): 3342-3352.
[8]	李盼, 马俊洋, 陈志豪, 王丽, 郭耘. Ru/α-MnO₂催化剂形貌对NH₃-SCO反应性能的影响[J]. 化工学报, 2023, 74(7): 2908-2918.
[9]	陈雅鑫, 袁航, 刘冠章, 毛磊, 杨纯, 张瑞芳, 张光亚. 蛋白质纳米笼介导的酶自固定化研究进展[J]. 化工学报, 2023, 74(7): 2773-2782.
[10]	汤晓玲, 王嘉瑞, 朱玄烨, 郑仁朝. 基于Pickering乳液的卤醇脱卤酶催化合成手性环氧氯丙烷[J]. 化工学报, 2023, 74(7): 2926-2934.
[11]	余娅洁, 李静茹, 周树锋, 李清彪, 詹国武. 基于天然生物模板构建纳米材料及集成催化剂研究进展[J]. 化工学报, 2023, 74(7): 2735-2752.
[12]	涂玉明, 邵高燕, 陈健杰, 刘凤, 田世超, 周智勇, 任钟旗. 钙基催化剂的设计合成及应用研究进展[J]. 化工学报, 2023, 74(7): 2717-2734.
[13]	张琦钰, 高利军, 苏宇航, 马晓博, 王翊丞, 张亚婷, 胡超. 碳基催化材料在电化学还原二氧化碳中的研究进展[J]. 化工学报, 2023, 74(7): 2753-2772.
[14]	张希庆, 王琰婷, 徐彦红, 常淑玲, 孙婷婷, 薛定, 张立红. Mg量影响的纳米片负载Pt-In催化异丁烷脱氢性能[J]. 化工学报, 2023, 74(6): 2427-2435.
[15]	张谭, 刘光, 李晋平, 孙予罕. Ru基氮还原电催化剂性能调控策略[J]. 化工学报, 2023, 74(6): 2264-2280.