5-氨基乙酰丙酸生物合成技术的发展及展望  

Advances and perspective on bioproduction of 5-aminolevulinic acid

作　　者：陈久洲[1] 王钰 蒲伟[1] 郑平[1] 孙际宾[1] CHEN Jiuzhou;WANG Yu;PU Wei;ZHENG Ping;SUN Jibin(Key Laboratory of Systems Microbial Biotechnology,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China)

机构地区：[1]中国科学院天津工业生物技术研究所,中国科学院系统微生物工程重点实验室,天津300308

出　　处：《合成生物学》2021年第6期1000-1016,共17页Synthetic Biology Journal

基　　金：国家重点研发计划(2018YFA0901400);国家自然科学基金(32000023)。

摘　　要：5-氨基乙酰丙酸(5-ALA)是生物体内天然存在的一种功能性非蛋白质氨基酸,在医药保健和农牧领域具有重要的应用价值。尽管化学合成技术率先打通了5-ALA的制备路线,但工艺的复杂性和高成本问题,限制了其生产规模和应用推广。随着生物技术的兴起,生物合成作为一种绿色替代技术成为解决上述问题的突破口。本文回顾了近50年来5-ALA生物合成技术的发展历程,综述了5-ALA生物合成的3种主要策略,即天然菌株诱变筛选、利用重组外源C4途径的工程菌株催化合成以及基于代谢工程的高效细胞工厂构建,总结了每种策略的技术特点和主要问题,重点介绍了代谢工程改造策略和合成生物技术在5-ALA微生物细胞工厂开发中的应用和研究进展。在此基础上,本文进一步分析了限制5-ALA生物合成的瓶颈,阐述了血红素合成代谢的复杂调控作用和多底物的协同供给在5-ALA生物合成中的重要作用,并从新靶点、新底盘和新技术策略的角度,对合成生物学时代5-ALA生物合成技术未来的发展进行了展望。As a functional non-proteinogenic amino acid,5-aminolevulinic acid(5-ALA)is naturally synthesized by microbes,plants,and animals.It is a precursor for biosynthesis of tetrapyrrole compounds,such as heme,porphyrin,chlorophyll,and vitamin B12.Because of the critical roles of tetrapyrrole compounds in cellular metabolism,5-ALA has gained increasing attention in the fields of medicine,health care,agriculture,and animal husbandry.Methods for chemical synthesis of 5-ALA have been established for decades and are the primary routes for industrial production of 5-ALA.However,the high complexity and relatively low yield of the synthesis process lead to the high price of 5-ALA,which seriously limits the production scale and its widespread applications,especially in the fields of agriculture and animal feed.As an alternative technology,bioproduction of 5-ALA from renewable resources holds great promise to simplify the production process and lower the production cost,and thus has received increasing attentions worldwide.Although some algae and photosynthetic bacteria are capable of synthesizing 5-ALA naturally,the production levels cannot meet the requirement of industrialization and commercialization.Moreover,these microorganisms are usually difficult to engineer due to lack of advanced genome editing tools.With the development of systems biology and synthetic biology approaches,intensive studies have focused on engineering platform microorganisms such as Escherichia coli and Corynebacterium glutamicum for 5-ALA bioproduction.Despite many successes in engineering synthetic 5-ALA producing strains,challenges remain in improving the production indices(titer,yield,and productivity)to levels as high as those for some proteinogenic amino acids,such as lysine and glutamate.In this paper,we review the development history of 5-ALA bioproduction technologies in the last half century and summarize the three key strategies for strain development and improvement,including mutagenesis and screening of natural strains,production by Escher

关 键 词：5-氨基乙酰丙酸 生物合成 代谢工程 合成生物学 微生物细胞工厂 

分 类 号：Q81[生物学—生物工程]