From single-enzyme catalysis to multienzyme cascade： inspired from Professor Daniel I.C. Wang’s pioneer work in enzyme technology

WU Shuke; ZHOU Yi; WANG Wen; ZHANG Wei; GAO Pengfei; LI Zhi

doi:10.12211/2096-8280.2021-004

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From single-enzyme catalysis to multienzyme cascade： inspired from Professor Daniel I.C. Wang’s pioneer work in enzyme technology

Invited Review | 更新时间：2026-03-05

- From single-enzyme catalysis to multienzyme cascade： inspired from Professor Daniel I.C. Wang’s pioneer work in enzyme technology
- Synthetic Biology Journal Vol. 2, Issue 4, Pages: 543-558(2021)
- 作者机构：
  
  1.华中农业大学生命科学技术学院，湖北武汉 430070
  2.雀巢新加坡研发中心，新加坡　619625
  3.新加坡科技研究局（A*STAR）生物过程技术研究所，新加坡 138668
  4.葛兰素史克中国投资有限公司，北京 100025
  5.新加坡国立大学化学与分子工程系，新加坡 117585
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2021-004
  CLC： Q814
- Received：12 January 2021，
  
  Revised：2021-03-17，
  
  Published：31 August 2021
- 稿件说明：
移动端阅览
吴淑可，周颐，王文，张巍，高鹏飞，李智. 从单酶催化到多酶级联催化——从王义翘教授在酶技术领域的贡献说开去［J］. 合成生物学， 2021， 2（4）： 543-558

WU Shuke， ZHOU Yi， WANG Wen， ZHANG Wei， GAO Pengfei， LI Zhi. From single-enzyme catalysis to multienzyme cascade： inspired from Professor Daniel I.C. Wang’s pioneer work in enzyme technology［J］. Synthetic Biology Journal， 2021， 2（4）： 543-558
吴淑可，周颐，王文，张巍，高鹏飞，李智. 从单酶催化到多酶级联催化——从王义翘教授在酶技术领域的贡献说开去［J］. 合成生物学， 2021， 2（4）： 543-558 DOI： 10.12211/2096-8280.2021-004.

WU Shuke， ZHOU Yi， WANG Wen， ZHANG Wei， GAO Pengfei， LI Zhi. From single-enzyme catalysis to multienzyme cascade： inspired from Professor Daniel I.C. Wang’s pioneer work in enzyme technology［J］. Synthetic Biology Journal， 2021， 2（4）： 543-558 DOI： 10.12211/2096-8280.2021-004.

摘要

作为国际生物工程和生物技术领域的奠基人和业界泰斗，麻省理工学院王义翘教授几十年来的研究涵盖了生化工程的上、中、下游的众多方向。在酶技术领域，他在早期就完成了几项标志性的工作，例如鱼蛋白的酶消化、甲醇氧化酶的固定化、无细胞多酶合成、非水相酶催化等。从2005年开始，王教授在十年间通过新加坡-麻省理工联盟（Singapore-MIT Alliance）项目和新加坡国立大学李智教授联合指导了数名博士生，并在酶技术的几个子方向上取得了重要成果，包括：①开发了酶固定化的方法用于构建高活力可回收的磁性纳米生物催化剂；②探索了P450单加氧化酶在水相-离子液体体系中的不对称亚砜化反应；③开发了基于通透全细胞的辅酶NADPH再生系统；④成功开发了模块化的多酶级联催化合成高值手性化合物，显著拓展了多酶级联催化的复杂度。其中，多酶级联催化因其“一锅法”的合成特性，避免额外的单元操作，节省人力、物力的投入和废弃物的产生等特点，近年来已经成为酶技术领域的研究热点。在介绍王教授相关工作之余，本文还总结了多酶级联催化在合成手性化合物和大宗化学品方面的最新进展，讨论了其未来的发展方向，并就其进一步整合合成生物学以及王教授所践行的定量化和工程化的理念进行了展望。

Abstract

As the founder and pioneer in the fields of bioengineering and biotechnology

Professor Daniel I. C. Wang at the Massachusetts Institute of Technology (MIT) had made tremendous contributions in many aspects in the up-

mid- and downstream of biochemical engineering for over 50 years. In the area of enzyme technology

he had impell several significant advances from the 1970s to 1990s

such as enzymatic digestion of fish protein

immobilization of methanol oxidase

cell-free multi-enzyme synthesis

and enzyme catalysis in organic medium

etc

. From 2005 to 2015 through the Singapore-MIT Alliance Program

Prof. Wang had jointly supervised several PhD students with Prof. Li Zhi at the National University of Singapore

and achieved important contributions biocatalysis

including: 1) developed enzyme immobilization methods for fabrication of highly active and recyclable magnetic nano-biocatalysts; 2) explored P450 monooxygenase for asymmetric sulfur oxidation in aqueous phase-ionic liquid systems; 3) developed an NADPH regeneration system based on permeabilized whole cells; 4) successfully developed modular multi-enzyme cascade catalysis to synthesize high-value chiral compounds

which significantly expanded the realm of biocatalysis. Among them

multi-enzyme cascade catalysis has become a research hotspot in the fi

eld of enzyme technology

due to its several desirable features

including the possibility of retrosynthetic design of various synthetic routes

the facile one-pot synthesis of final products

the reduction of additional unit operations

the saving of inputs from manpower and materials

and the minimization of waste generation. In this account

we also review the latest progress of multi-enzyme cascades for the synthesis of chiral compounds (

e.g

chiral amines

amino acids) and bulk chemicals (

e.g

precursors for polymers)

and discuss its future development directions. Last but not the least

we provide an outlook for integrating multi-enzyme cascades with synthetic biology

and thus assembling biochemical reactions together with quantitative analysis and engineering concepts

as advocated by Prof. Wang throughout his scientific career.

关键词

Keywords

references

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