代谢工程改造酵母生产多不饱和脂肪酸的研究进展

doi:10.16085/j.issn.1000-6613.2016.03.034

化工进展 ›› 2016, Vol. 35 ›› Issue (03): 872-878.DOI: 10.16085/j.issn.1000-6613.2016.03.034

代谢工程改造酵母生产多不饱和脂肪酸的研究进展

孙美莉, 刘虎虎, 邬文嘉, 任路静, 黄和, 纪晓俊

南京工业大学生物与制药工程学院, 材料化学工程国家重点实验室, 江苏南京 211816

收稿日期:2015-07-30 修回日期:2015-08-13 出版日期:2016-03-05 发布日期:2016-03-05
通讯作者: 纪晓俊,副教授,研究方向为微生物代谢工程。E-mail:xiaojunji@njtech.edu.cn.
作者简介:孙美莉(1990-),女,硕士研究生。
基金资助:
国家自然科学基金(21376002,21476111)、江苏省自然科学基金(BK20131405)、国家高技术研究发展计划(2014AA021703)及江苏高校优势学科建设工程项目。

Metabolic engineering of yeast to produce polyunsaturated fatty acids

SUN Meili, LIU Huhu, WU Wenjia, REN Lujing, HUANG He, JI Xiaojun

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech. University, Nanjing 211816, Jiangsu, China

Received:2015-07-30 Revised:2015-08-13 Online:2016-03-05 Published:2016-03-05

摘要/Abstract

摘要： 多不饱和脂肪酸因其在食品和医药领域的广泛作用而得到人们极大的关注,当前利用微生物发酵生产多不饱和脂肪酸具有诸多优点,由于酵母生产迅速且生物量较高,利用酵母生产多不饱和脂肪酸已成为人们关注的热点。本文综述了代谢工程改造酵母生产多不饱和脂肪酸的研究进展,以常规酵母-酿酒酵母和非常规酵母- 解脂耶氏酵母为例,介绍了酵母菌中多不饱和脂肪酸的代谢途径、酵母产油脂的生化机制、代谢工程改造酵母产多不饱和脂肪酸以及不饱和脂肪酸积累对酵母耐受性的影响。以后研究工作的重点是进一步加强对酵母生产多不饱和脂肪酸的机理研究,并以此为来指导代谢工程改造酵母生产多不饱和脂肪酸。

关键词: 多不饱和脂肪酸, 酿酒酵母, 解脂耶氏酵母, 代谢途径, 代谢工程

Abstract: Polyunsaturated fatty acids,which play important role in food and medicine and other fields,have gained great attention in recent years. The process for production of polyunsaturated fatty acids by microorganism has its own advantages. Yeast,which has rapid growth and accumulation rate, has become the research spotlight and this work reviews the metabolic engineering of yeast to produce polyunsaturated fatty acids. The biosynthetic pathway of polyunsaturated fatty acids,biochemistry mechanism of lipid accumulation , polyunsaturated fatty acids production through metabolic engineering and the effect of unsaturated fatty acids on yeast tolerance,especially in the model organism of Saccharomyces cerevisiae and non-conventional yeast of Yarrowia lipolytica,were addressed. Future research should be focused on exploring the mechanism of polyunsaturated fatty acids production with yeast ,which would guide metabolic engineering of yeast to produce polyunsaturated fatty acids.

Key words: polyunsaturated fatty acids, Saccharomyces cerevisiae, Yarrowia lipolytica, metabolic engineering, biosynthetic pathway

中图分类号:

Q939.97

孙美莉, 刘虎虎, 邬文嘉, 任路静, 黄和, 纪晓俊. 代谢工程改造酵母生产多不饱和脂肪酸的研究进展[J]. 化工进展, 2016, 35(03): 872-878.

SUN Meili, LIU Huhu, WU Wenjia, REN Lujing, HUANG He, JI Xiaojun. Metabolic engineering of yeast to produce polyunsaturated fatty acids[J]. Chemical Industry and Engineering Progree, 2016, 35(03): 872-878.

参考文献

[1] JANSSEN C I,KILIAAN A J. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence:the influence of LCPUFA on neural development,aging,and neurodegeneration[J]. Progress in Lipid Research,2014,53:1-17.

[2] FUNK C D. Prostaglandins and leukotrienes:advances in eicosanoid biology[J]. Science,2001,294:1871-1875.

[3] BEOPOULOS A,CESCUT J,HADDOUCHE R,et al. Yarrowia lipolytica as a model for bio-oil production[J]. Progress in Lipid Research,2009,48:375-387.

[4] JI X J,REN L J,NIE Z K,et al. Fungal arachidonic acid-rich oil: research,development and industrialization[J]. Critical Reviews in Biotechnology,2014,34:197-214.

[5] UEMURA H. Synthesis and production of unsaturated and polyunsaturated fatty acids in yeast:current state and perspectives[J]. Applied Microbiology and Biotechnology,2012,95:1-12.

[6] XUE Z,SHARPE P L,HONG S P,et al. Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica[J]. Nature Biotechnology,2013,31:734-740.

[7] ZHANG H,ZHANG L,CHEN H,et al. Enhanced lipid accumulation in the yeast Yarrowia lipolytica by over-expression of ATP:citrate lyase from Mus musculus[J]. Journal of Biotechnology,2014,192 Pt A:78-84.

[8] GONG Y,WAN X,JIANG M,et al. Metabolic engineering of microorganisms to produce omega-3 very long-chain polyunsaturated fatty acids[J]. Progress in Lipid Research,2014,56C:19-35.

[9] DYER J M,CHAPITAL D C,KUAN J W,et al. Metabolic engineering of Saccharomyces cerevisiae for production of novel lipid compounds[J]. Applied Microbiology and Biotechnology,2002, 59:224-230.

[10] HOLIC R,YAZAWA H,KUMAGAI H,et al. Engineered high content of ricinoleic acid in fission yeast Schizosaccharomyces pombe[J]. Applied Microbiology and Biotechnology,2012,95: 179-187.

[11] SALUNKE D,MANGLEKAR R,GADRE R, et al. Production of polyunsaturated fatty acids in recombinant Lipomyces starkeyi through submerged fermentation[J]. Bioprocess and Biosystems Engineering,2015,38:1407-1414.

[12] BRAUNWALD T,SCHWEMMLEIN L,GRAEFF-HONNINGER S, et al. Effect of different C/N ratios on carotenoid and lipid production by Rhodotorula glutinis[J]. Applied Microbiology and Biotechnology,2013,97:6581-6588.

[13] GALAFASSI S,CUCCHETTI D,PIZZA F,et al. Lipid production for second generation biodiesel by the oleaginous yeast Rhodotorula graminis[J]. Bioresource Technology,2012,111:398-403.

[14] LI Y H,LIU B, BAI F W,et al. Optimized culture medium and fermentation conditions for lipid production by Rhodosporidium toruloides[J]. Chinese Journal of Biotechnology,2006,22:650-656.

[15] RUENWAI R,NEISS A,LAOTENG K,et al. Heterologous production of polyunsaturated fatty acids in Saccharomyces cerevisiae causes a global transcriptional response resulting in reduced proteasomal activity and increased oxidative stress[J]. Biotechnology Journal,2011,6:343-356.

[16] CHUANG L T,LEONARD A E,LIU J W,et al. Inhibitory effect of conjugated linoleic acid on linoleic acid elongation in transformed yeast with human elongase[J]. Lipids,2001,36:1099-1103.

[17] BEAUDOIN F,MICHAELSON L V,HEY S J,et al. Heterologous reconstitution in yeast of the polyunsaturated fatty acid biosynthetic pathway[J]. Proceedings of the National Academy of Sciences of the United States of America,2000,97:6421-6426.

[18] YAZAWA H,IWAHASHI H,KAMISAKA Y,et al. Production of polyunsaturated fatty acids in yeast Saccharomyces cerevisiae and its relation to alkaline pH tolerance[J]. Yeast,2009,26:167-184.

[19] YAZAWA H,IWAHASHI H,KAMISAKA Y,et al. Heterologous production of dihomo-gamma-linolenic acid in Saccharomyces cerevisiae[J]. Applied Environment Microbiology , 2007 , 73 : 6965-6971.

[20] WYNN J P,HAMID A B A,RATLEDGE C. The role of malic enzyme in the regulation of lipid accumulation in filamentous fungi[J]. Microbiology-UK,1999,145:1911-1917.

[21] DULERMO T,LAZAR Z,DULERMO R,et al. Analysis of ATP-citrate lyase and malic enzyme mutants of Yarrowia lipolytica points out the importance of mannitol metabolism in fatty acid synthesis[J]. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids,2015,1851:1107-1117.

[22] WASYLENKO T M,AHN W S,STEPHANOPOULOS G. The oxidative pentose phosphate pathway is the primary source of NADPH for lipid overproduction from glucose in Yarrowia lipolytica[J]. Metabolic Engineering,2015,30:27-39.

[23] MATSAKAS L,BONTURI N,MIRANDA E A,et al. High concentrations of dried sorghum stalks as a biomass feedstock for single cell oil production by Rhodosporidium toruloides[J]. Biotechnology for Biofuels,2015,8:6-12.

[24] LIU L,PAN A,SPOFFORD C,et al. An evolutionary metabolic engineering approach for enhancing lipogenesis in Yarrowia lipolytica[J]. Metabolic Engineering,2015,29:36-45.

[25] TAI M,STEPHANOPOULOS G. Engineering the push and pull of lipid biosynthesis in oleaginous yeast Yarrowia lipolytica for biofuel production[J]. Metabolic Engineering,2013,15:1-9.

[26] LAZAR Z,DULERMO T,NEUVEGLISE C,et al. Hexokinase-a limiting factor in lipid production from fructose in Yarrowia lipolytica[J]. Metabolic Engineering,2014,26C:89-99.

[27] BEOPOULOS A,MROZOVA Z,THEVENIEAU F,et al. Control of lipid accumulation in the yeast Yarrowia lipolytica[J]. Applied Environment Microbiology,2008,74:7779-7789.

[28] XIE D,JACKSON E N,ZHU Q. Sustainable source of omega-3 eicosapentaenoic acid from metabolically engineered Yarrowia lipolytica:from fundamental research to commercial production[J]. Applied Microbiology and Biotechnology,2015,99:1599-1610.

[29] STEELS E L,LEARMONTH R P,WATSON K. Stress tolerance and membrane lipid unsaturation in Saccharomyces cerevisiae grown aerobically or anaerobically[J]. Microbiology,1994,140:569-576.

[30] 张强,郭元,韩德明. 酿酒酵母乙醇耐受性的研究进展[J]. 化工进展,2014,33(1):187-192.

[31] MA M,LIU Z L. Mechanisms of ethanol tolerance in Saccharomyces cerevisiae[J]. Applied Microbiology and Biotechnology,2010,87: 829-845.

[32] KAJIWARA S,SUGA K,SONE H,et al. Improved ethanol tolerance of Saccharomyces cerevisiae strains by increases in fatty acid unsaturation via metabolic engineering[J]. Biotechnology Letters, 2000,22:1839-1843.

[33] 邢建宇,李春荣,林挺花,等. 脂肪酸对酿酒酵母乙醇耐受性的影响[J]. 食品研究与开发,2009,30(6):33-35

[34] 李艾. 产油微生物利用废弃物积累油脂的研究进展[J]. 化工进展, 2015,34(6):1762-1767.

代谢工程改造酵母生产多不饱和脂肪酸的研究进展

Metabolic engineering of yeast to produce polyunsaturated fatty acids

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	赵同心, 赵磊, 张延平, 李寅. 甲酸微生物转化研究进展[J]. 化工进展, 2023, 42(1): 67-72.
[2]	陶雨萱, 郭亮, 高聪, 宋伟, 陈修来. 代谢工程改造微生物固定二氧化碳研究进展[J]. 化工进展, 2023, 42(1): 40-52.
[3]	郭峰, 张尚杰, 蒋羽佳, 姜万奎, 信丰学, 章文明, 姜岷. 一碳资源在酵母中的利用与转化[J]. 化工进展, 2023, 42(1): 30-39.
[4]	董晓宇. 酿酒酵母钙通道膜蛋白单克隆抗体制备及鉴定[J]. 化工进展, 2021, 40(S1): 334-343.
[5]	陶雨萱, 张尚杰, 景艺文, 信丰学, 董维亮, 周杰, 蒋羽佳, 章文明, 姜岷. 甲基营养型大肠杆菌构建策略的研究进展[J]. 化工进展, 2021, 40(7): 3932-3941.
[6]	包文君, 李子富, 王雪梅, 高瑞岭, 程世昆, 门玉. 产油酵母利用廉价原料合成油脂的研究进展[J]. 化工进展, 2021, 40(5): 2484-2495.
[7]	李玲, 于泳, 胡永红. 发酵法生产利普司他汀的研究进展[J]. 化工进展, 2021, 40(4): 2251-2257.
[8]	郭亮, 高聪, 张丽, 陈修来, 刘立明. 人工代谢路径适配性的研究进展[J]. 化工进展, 2021, 40(3): 1252-1261.
[9]	周子康, 许平. 全局转录调控在细胞工厂构建中的应用与进展[J]. 化工进展, 2021, 40(3): 1248-1251.
[10]	刘卫兵, 叶邦策. 放线菌聚酮类化合物的合成生物学研究及生物制造[J]. 化工进展, 2021, 40(3): 1226-1237.
[11]	高聪, 郭亮, 胡贵鹏, 陈修来, 刘立明. 微生物细胞工厂碳流调控进展[J]. 化工进展, 2021, 40(12): 6807-6817.
[12]	叶会科, 王秋珍, 何耀东, 汪光义. 破囊壶菌发酵生产DHA的研究进展[J]. 化工进展, 2020, 39(8): 3235-3245.
[13]	王晨,赵雨佳,李春,周晓宏. 动态转录调控微生物代谢途径研究进展[J]. 化工进展, 2019, 38(9): 4238-4246.
[14]	陈露,刘丁玉,汪保卫,赵玉姣,贾广韬,陈涛,王智文. 大肠杆菌乙酰辅酶A代谢调控及其应用研究进展[J]. 化工进展, 2019, 38(9): 4218-4226.
[15]	常鹏程, 于洋, 王颖, 李春. 酿酒酵母高效合成萜类化合物的组合调控策略[J]. 化工进展, 2019, 38(01): 598-605.