从制造到智造:维生素B_(12)与合成生物学的不解之缘  

From manufacturing to intelligent manufacturing:the symbiotic tale of synthetic biology and vitamin B_(12)

作　　者：康倩 吕荣玉 张大伟[1,2] Qian Kang;Rongyu Lv;Dawei Zhang(Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China;Key Laboratory of Engineering Biology for Low-Carbon Manufacturing,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China;School of Biological Engineering,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]中国科学院天津工业生物技术研究所,天津300308 [2]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 [3]天津科技大学生物工程学院,天津300457

出　　处：《科学通报》2025年第1期44-59,共16页Chinese Science Bulletin

基　　金：国家重点研发计划(2020YFA0907800);国家自然科学基金(22325807,22178372,22208367);中国博士后科学基金会与天津市联合资助项目(2023T008TJ)资助。

摘　　要：合成生物学以生命科学为基础,辅以工程化思维,融合了物理学、化学、计算机科学等学科知识,旨在改造、设计、构建新型的生物体系.维生素B_(12)作为横跨医学、化学和生物学三学科的“明星小分子”,近百年来一直备受研究人员的重视,其生物制造在合成生物学发展的推动下不断创新.本文探讨了自1926年维生素B_(12)小分子被发现至今的重要研究成果和内容,其中囊括在早期医学、化学研究时期,维生素B_(12)相关研究的重要诺奖级成果;天然合成维生素B_(12)菌株挖掘、催化途径解析及遗传工具开发;人工重组合成维生素B_(12)菌株和体系的构建及优化等重要内容.聚焦近30年来,合成生物学系统研究方法的提出和推进对维生素B_(12)生物制造有显著促进作用.这些进展推动了维生素B_(12)从简单的天然菌种“制造”过程走向更具设计性、智能化的人工菌种与人工体系的“智造”过程转变.此外,维生素B_(12)复杂的天然合成途径成为经典的研究范本,为合成生物学发展提供了优秀的经典案例,与合成生物学的发展结下“不解之缘”.Synthetic biology,which approaches biotechnological problems with an engineering mindset,integrates knowledge from disciplines such as physics,chemistry,and computer science,aiming to transform,design,and construct novel biological systems.This interdisciplinary field is distinct in its systematic,modular,and design-oriented methodology,which contrasts with the more traditional trial-and-error techniques of biology.By applying engineering principles,synthetic biology enables precise manipulation and optimization of biological processes,leading to significant advancements in biotechnology.One particularly valuable compound that has benefited from this approach is vitamin B_(12).Vitamin B_(12)is a valuable compound with diverse applications in medicine,chemistry,and biology,which has inspired continuous research for nearly a century.Early breakthroughs in vitamin B_(12)research,especially those related to its chemical structure and biological functions,earned several Nobel Prizes and contributed to fundamental knowledge in medical and chemical fields.Currently,the production of vitamin B_(12) has traditionally relied on natural microbial strains,which synthesize the compound through complex biochemical pathways.Recently,its biotechnological production has received a fresh impetus due to advances of synthetic biology.This paper explores the important achievements of vitamin B_(12) research since its discovery in 1926,including the Nobel prize-winning achievements during the early periods of medical and chemical investigation,which laid the groundwork for understanding the compound's structure and function.Additionally,since the 1980s,the isolation of naturally occurring strains that synthesize vitamin B_(12),along with the analysis of their catalytic pathways,has sparked a surge of interest in the biotechnological production of vitamin B_(12).Subsequently,the development of genetic tools of natural strains capable of synthesizing vitamin B_(12) has significantly advanced its biosynthetic production.Recently,construc

关 键 词：合成生物学 维生素B_(12) 生物制造 细胞工厂 无细胞合成 

分 类 号：Q81[生物学—生物工程]