合成生物学驱动非天然产物的光生物合成

许嘉凡; 周佳海; 高江涛; 古阳

doi:10.12211/2096-8280.2026-009

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合成生物学驱动非天然产物的光生物合成

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- 合成生物学驱动非天然产物的光生物合成
- Synthetic biology drives photosynthetic production of unnatural compounds
- 合成生物学 2026年页码：1-7
- 作者机构：
  
  1.福建农林大学生命科学学院，福建福州 350002
  2.中国科学院深圳先进技术研究院，定量合成生物学全国重点实验室，广东深圳 518055
  3.南京师范大学微生物改造技术全国重点实验室，江苏南京 210023
- 作者简介：
  
  许嘉凡（2001—），男，硕士研究生。研究方向为光酶催化的非天然反应。
  周佳海（1972—），男，研究员，博士生导师。研究方向是工业生物技术、合成生物学相关的微生物酶学以及活性天然产物的化学生物学，通过会聚酶学、结构生物学及蛋白质理性设计等技术方法，重点研究酶的结构与催化机理、定向进化酶的科学规律、分子智能设计等。
  高江涛（1978—），男，福建农林大学蜂学与生物医药学院副院长，闽江学者特聘教授，博士生导师，2010-2014年于美国伊利诺伊大学香槟分校进行博士后研究（合作导师：美国科学院院士Professor Wilfred van der Donk， Professor Huimin Zhao）。主要研究兴趣为天然药物的合成生物学及化学生物学，主持国家自然基金联合基金重点项
  古阳（1989—），男，副研究员，博士生导师。研究方向是将化学合成的多样性与生物合成的精准性相结合，通过跨学科的研究方法，设计并改造具有非天然反应活性的人工金属酶，以突破天然酶的化学反应空间，从而实现对功能分子的精准构建。
- 基金信息：
  
  广东省重点领域研发计划(2024B1111160007);国家自然科学基金(22201295);深圳市自然科学基金(JCYJ20220818100804010);国家重点研发计划(2021YFA0910500)
- DOI：10.12211/2096-8280.2026-009
  中图分类号： Q816
- 收稿：2026-03-02，
  
  修回：2026-03-18，
  
  网络首发：2026-04-08，
- 稿件说明：
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许嘉凡，周佳海，高江涛，古阳. 合成生物学驱动非天然产物的光生物合成［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-009

XU Jiafan， ZHOU Jiahai， GAO Jiangtao， GU Yang. Synthetic biology drives photosynthetic production of unnatural compounds［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-009
许嘉凡，周佳海，高江涛，古阳. 合成生物学驱动非天然产物的光生物合成［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-009 DOI：

XU Jiafan， ZHOU Jiahai， GAO Jiangtao， GU Yang. Synthetic biology drives photosynthetic production of unnatural compounds［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-009 DOI：

摘要

光生物催化是一种整合了光催化和生物合成的强大合成策略，能够驱动许多非天然反应。然而，其规模化应用受限于酶载量高、辅因子昂贵以及反应稳定性差等问题。近期，伊利诺伊大学厄巴纳-香槟分校的赵惠民团队利用合成生物学技术成功将光酶反应整合到细菌的代谢通路中，构建了首个能够通过发酵放大生产非天然产物的大肠杆菌“生产工厂”。该技术成功实现了对苯酚-吲哚类化合物4-（2-（3a，7a-二氢-1H-吲哚-3-基）乙基）苯酚（DIEP）的完全生物合成。该研究不仅展示了光酶反应在活细胞中实现完全生物合成和工程化放大的可能性，还验证了所合成的非天然产物具有生物活性，这表明该技术具有工业应用潜力。本文将介绍该研究成果，并结合相关研究工作提出见解，以期推动光生物催化从概念验证迈向工业生产。

Abstract

Photobiocatalysis is a synthetic strategy that integrates photocatalysis and biosynthesis

and has the capacity to drive numerous non-natural reactions. However

its large-scale application is constrained by issues such as high enzyme loading

expensive cofactors

and poor reaction stability. Recently

the research team led by Hui-Min Zhao at the University of Illinois Urbana-Champaign achieved a significant milestone in synthetic biology by successfully integrating photoenzymatic reactions into bacterial metabolic pathways. This pioneering advancement

reported in the scientific community

has established the first "E. coli production factory" capable of amplifying the production of unnatural products through the process of fermentation. This technology has been demonstrated to be capable of synthesising the phenol-indole compound 4-(2-(3a

7a-dihydro-1H-indol-3-yl)ethyl)phenol (DIEP) in its complete biosynthetic form. This research demonstrates not only the feasibility of achieving complete biosynthesis and engineered amplification of photoenzymatic reactions within living cells

but also validates the biological activity of the synthesized non-natural product

indicating the technology's industrial application potential. The present paper sets out the research findings and offers insights based on related studies

with a view to advancing photobiocatalysis from the proof-of-concept stage towards industrial production.

关键词

Keywords

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