ω-氨基酸与内酰胺的生物合成研究进展

刘益宁; 蒲伟; 杨金星; 王钰

doi:10.12211/2096-8280.2024-019

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ω-氨基酸与内酰胺的生物合成研究进展

特约评述 | 更新时间：2025-04-11

- ω-氨基酸与内酰胺的生物合成研究进展
- Recent advances in the biosynthesis of ω-amino acids and lactams
- 合成生物学 2024年5卷第6期页码：1350-1366
- 作者机构：
  
  1.中国科学院天津工业生物技术研究所，低碳合成工程生物学重点实验室，天津 300308
  2.国家合成生物技术创新中心，天津 300308
  3.内江师范学院生命科学学院，四川内江 641100
  4.四川省高等学校特色农业资源研究与利用重点实验室，四川内江 641100
  5.华南理工大学生物科学与工程学院，广东广州 510006
- 作者简介：
  
  [ "刘益宁（1996—），女，硕士，科研助理。研究方向为系统代谢工程与合成生物学。E-mail：liuyn@tib.cas.cn" ]
  [ "蒲伟（1988—），男，博士，讲师。研究方向为系统代谢工程与合成生物学。E-mail：puwei1988@outlook.com" ]
  [ "王钰（1987—），男，博士，研究员，博士生导师。研究方向为工业微生物的基因编辑育种和一碳原料的生物转化利用研究。E-mail：wang_y@tib.cas.cn" ]
- 基金信息：
  
  中国科学院关键核心技术攻坚先导专项(XDC0110201)
- DOI：10.12211/2096-8280.2024-019
  中图分类号： Q816
- 收稿：2024-02-04，
  
  修回：2024-04-25，
  
  纸质出版：2024-12-31
- 稿件说明：
移动端阅览
刘益宁，蒲伟，杨金星，王钰. ω-氨基酸与内酰胺的生物合成研究进展［J］. 合成生物学， 2024， 5（6）： 1350-1366

LIU Yining， PU Wei， YANG Jinxing， WANG Yu. Recent advances in the biosynthesis of ω-amino acids and lactams［J］. Synthetic Biology Journal， 2024， 5（6）： 1350-1366
刘益宁，蒲伟，杨金星，王钰. ω-氨基酸与内酰胺的生物合成研究进展［J］. 合成生物学， 2024， 5（6）： 1350-1366 DOI： 10.12211/2096-8280.2024-019.

LIU Yining， PU Wei， YANG Jinxing， WANG Yu. Recent advances in the biosynthesis of ω-amino acids and lactams［J］. Synthetic Biology Journal， 2024， 5（6）： 1350-1366 DOI： 10.12211/2096-8280.2024-019.

摘要

以可再生碳资源为原料，以工程微生物为核心工具，通过生物制造的方式生产生物基材料等化学品，具有绿色、低碳的优势，已经成为目前研究的热点。ω-氨基酸是氨基和羧基分别位于支链碳链两端的一种非天然氨基酸，其自身环化的产物内酰胺是合成聚酰胺材料（又名尼龙）的关键单体。聚酰胺材料具有广泛的应用与巨大的市场，目前主要通过石化路线生产，生物合成路线仍处于研究阶段，但是近年来进展迅速。本文系统介绍了ω-氨基酸与内酰胺的生物合成研究进展。为合成生物基聚酰胺材料，研究者设计了ω-氨基酸的人工合成途径，挖掘了可环化ω-氨基酸合成内酰胺的关键酶，通过在微生物底盘细胞中组装合成途径，调控和优化代谢流量，开发内酰胺生物传感器并进行高通量筛选，实现了C

～C

的ω-氨基酸和内酰胺的生物合成。尤其以葡萄糖为原料合成戊内酰胺的产量超过70 g/L，生产强度达到约1 g/（L·h），接近可工业化的水平。最后，本文也讨论了目前ω-氨基酸与内酰胺生物合成面临的途径原子经济性低、关键环化酶限速、一碳等非粮原料开发利用不足等挑战。

Abstract

Increasing petroleum consumption and growing environmental concerns necessitate the sustainable production of chemicals and fuels from renewable resources. By utilizing renewable resources as raw materials and engineered microorganisms as the core tools

the bio-manufacturing of bio-based materials has become a hot research topic due to its green and low-carbon advantages. ω-Amino acids are a type of non-natural amino acids with amino and carboxyl groups located at the ends of the straight carbon chain. Self-cyclization of ω-amino acids produce lactams

which are the key monomers for the synthesis

of polyamide materials

commonly known as nylon. Polyamide materials have wide applications and a huge global market over seven million tons per year. Nowadays

polyamide materials and their monomers are primarily produced through petrochemical routes with non-renewable resources. The research on biosynthesis of these materials and monomers is still in the early stages

but significant progress has been made in recent years. This review article systematically introduces the recent advances in the biosynthesis of ω-amino acids and lactams. To achieve the bio-manufacturing of bio-based polyamide materials

researchers have designed artificial biosynthetic pathways for ω-amino acids from renewable carbon sources such as glucose. The key enzymes for the cyclization of ω-amino acids to form lactams have been identified. By assembling the biosynthetic pathway in microbial chassis such as

Escherichia coli

and

Corynebacterium glutamicum

production of ω-amino acids and lactams have been achieved. Furthermore

the metabolic flux was fine-tuned by regulating and optimizing the expression of key genes to improve the biosynthesis of ω-amino acids and lactams. Besides

biosensors of lactams have been developed to transfer the intracellular concentrations of lactams into easily detectable signals such as fluorescence. Such biosensors have been successfully used for high-throughput screening of ω-amino acid cyclization enzymes and dynamic regulation of biosynthetic pathway. These effects have resulted in the successful biosynthesis of C

-C

ω-amino acids and lactams. Particularly

using glucose as a raw material

the production of valerolactam by fed-batch fermentation exceeded 70 g/L

with a productivity of about 1 g/(L·h)

which approaches the level required for industrialization and commercialization. Finally

the review article discusses the current challenges faced in the biosynthesis of ω-amino acids and lactams

including the low yield of biosynthetic pathways

rat

e-limitations posed by key cyclization enzymes

and insufficient utilization of non-food carbon sources such as one-carbon compounds.

关键词

Keywords

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