合成生物学 ›› 2021, Vol. 2 ›› Issue (6): 902-919.DOI: 10.12211/2096-8280.2021-049

• 特约评述 • 上一篇    下一篇

人工代谢途径合成有机醇有机酸的研究进展

曹晨凯, 李佳隆, 张科春   

  1. 西湖大学工学院,浙江省海岸带环境与资源研究重点实验室,浙江  杭州  310024
  • 收稿日期:2021-04-23 修回日期:2021-11-19 出版日期:2021-12-31 发布日期:2022-01-21
  • 通讯作者: 张科春
  • 作者简介:曹晨凯(1996—),男,博士研究生。研究方向为代谢工程。E-mail:caochenkai@westlake.edu.cn|李佳隆(1996—),男,博士研究生。研究方向为代谢工程。E-mail:lijialong@westlake.edu.cn|张科春(1978—),特聘研究员,博士生导师。研究方向为应用合成生物、绿色化学、材料科学和工程优化的方法,设计绿色新化工生产路线和开发环保新材料,为循环经济向前发展提供新的解决方案。E-mail:zhangkechun@westlake.edu.cn
  • 基金资助:
    国家自然科学基金(22078267)

Progress in artificial metabolic pathways for biosynthesis of organic alcohols & acids

Chenkai CAO, Jialong LI, Kechun ZHANG   

  1. Key Laboratory of Coastal Environment and Resources of Zhejiang Province,School of Engineering,Westlake University,Hangzhou 310024,Zhejiang,China
  • Received:2021-04-23 Revised:2021-11-19 Online:2021-12-31 Published:2022-01-21
  • Contact: Kechun ZHANG

摘要:

有机酸有机醇不仅是食品、化工、医药领域的原料,更是一类重要的生物基燃料,相比于传统的石油基燃料,具有原料可再生,生产过程清洁的特点,是应对能源危机、环境污染问题的有效对策。传统的代谢工程方法是通过在微生物中过表达产物相关的特异性酶实现的,应用时常有发酵原料单一,代谢效率不高,产物种类受限等问题。筛选并重新组合不同来源的酶来构建人工代谢途径是一个有效的解决方案,同时也是代谢工程方法发展的一个重要趋势。本文综述了近年来构建人工代谢途径生产有机酸有机醇取得的突破与进展,具体阐述了5种创新生物合成途径(一碳化合物同化途径、非磷酸化途径、酮酸途径、β-氧化逆循环途径和聚酮化合物途径)的相关机理,为未来构建低成本、高效、产物多样化的有机酸有机醇生物合成平台提供了可能。

关键词: 有机酸, 有机醇, 生物基燃料, 代谢工程, 人工代谢途径

Abstract:

Organic acids and alcohols are usually known as commercial feedstock in chemical engineering and pharmaceutical field. It is also known as potential significant biofuel. Compared with traditional fossil fuels, the characteristics of industrial application of organic acids and alcohols can provide great advantages such as renewable feedstock and green production process. They are effective countermeasures to deal with energy crisis and environmental pollution. Traditional metabolic engineering is realized by overexpression specific genes to elevate the corresponding enzyme level. With certain artificial genetic transformation and modification, a microbial cell factory can be constructed for efficient production of certain organic acids and alcohols. However, problems such as limited fermentation raw materials, low metabolic efficiency, and limited product types arise during practical implementation. Constructing artificial metabolic pathways through screening and recombining nonhomologous enzymes can become an effective solution, which is also a cutting-edge general trend in this field. In this paper, recent breakthroughs and progress in constructing artificial metabolic pathway to produce organic acids and alcohols are reviewed. Five novel biosynthetic pathways are expounded with details including C1 compounds assimilation pathway, nonphosphorylation pathway, ketoacid/ammino acid pathway, RBO pathway (reversal of β-oxidation pathway), and PKS pathway (polyketide pathway). Furthermore, the advantages and limitations compared with traditional chemical-produced technique are also discussed. Potential problems such as the tolerance of one carbon compounds, the inefficient conversion of xylose, the inefficient catalysis of key enzyme reactions in ketoacid amino acid pathway, and the lack of diversity of RBO pathway and PKS pathway products are reported in respected to practical application of the technology. In conclusion, the feasibility of establishing new metabolic pathways for production of specific products is analyzed, which has the potential of providing the possibility for the construction of high cost-efficient and diversified organic acid and organic alcohol biosynthesis platform in the future.

Key words: organic acid, organic alcohol, biofuel, metabolic engineering, artificial metabolic pathway

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