BioHPP<sup>®</sup>: a benchmark of biomanufacturing for high optically pure L-phosphinothricin

CHENG Feng; ZOU Shuping; XU Jianmiao; TANG Heng; XUE Yaping; ZHENG Yuguo

doi:10.12211/2096-8280.2024-032

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BioHPP^®: a benchmark of biomanufacturing for high optically pure L-phosphinothricin

Invited Review | 更新时间：2025-04-11

- BioHPP^®: a benchmark of biomanufacturing for high optically pure L-phosphinothricin
- Synthetic Biology Journal Vol. 5, Issue 6, Pages: 1404-1418(2024)
- 作者机构：
  
  1.浙江工业大学生物工程学院，全省生物有机合成重点实验室，浙江杭州 310014
  2.浙江工业大学，手性生物制造国家地方联合工程研究中心，浙江杭州 310014
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-032
  CLC： Q81
- Received：02 April 2024，
  
  Revised：2024-06-25，
  
  Published：31 December 2024
- 稿件说明：
移动端阅览
程峰，邹树平，徐建妙，汤恒，薛亚平，郑裕国. 生物高纯精草：高光学纯L-草铵膦生物制造的创新与发展［J］. 合成生物学， 2024， 5（6）： 1404-1418

CHENG Feng， ZOU Shuping， XU Jianmiao， TANG Heng， XUE Yaping， ZHENG Yuguo. BioHPP^®： a benchmark of biomanufacturing for high optically pure L-phosphinothricin［J］. Synthetic Biology Journal， 2024， 5（6）： 1404-1418
程峰，邹树平，徐建妙，汤恒，薛亚平，郑裕国. 生物高纯精草：高光学纯L-草铵膦生物制造的创新与发展［J］. 合成生物学， 2024， 5（6）： 1404-1418 DOI： 10.12211/2096-8280.2024-032.

CHENG Feng， ZOU Shuping， XU Jianmiao， TANG Heng， XUE Yaping， ZHENG Yuguo. BioHPP^®： a benchmark of biomanufacturing for high optically pure L-phosphinothricin［J］. Synthetic Biology Journal， 2024， 5（6）： 1404-1418 DOI： 10.12211/2096-8280.2024-032.

摘要

草铵膦是全球三大除草剂之一，具有广谱、高活性、非选择性等特点，市场前景被广泛看好。然而，草铵膦具有两种对映异构体（

型和

型），其除草活性主要来自于其中的

L型对映体（L-

草铵膦）。因此，高光学纯

L-

草铵膦高效合成至关重要。本文作者团队者研究团队在中国“生物农药之父”沈寅初院士的指导下，开展生物合成

L-

草铵膦的科学研究和产业化实践长达二十余年，涵盖合成路线重构、生物无机胺化技术建立、生物催化剂创制、产物分离纯化、反应装备、过程智能化控制等方面，开发了“生物高纯精草生产技术”（BioHPP

），建成了万吨级

L-

草铵膦数字智能化生产线，利用智能传感器和执行器，实现超千个控制点的实时数据采集、传输、分析和反馈调节，全自动化参数采集与控制生产效率提高50%，劳动强度降低70%以上，实现了万吨级

L-

草铵膦的生物智能制造。本文在研究团队长期积累的基础上，总结和分析了

，

-草铵膦主流生产工艺路线，详述了创新

生物制造技术、合成生物技术构筑

L-

草铵膦关键合成体系的原理和方法，从底物合成与选择、生物催化剂类型、氨基供体使用、分离纯化等方面比较了这些路线的各自特点及实现产业化的关键要点。可以预见，在合成生物技术的助力下，未来将有越来越多的高光学纯度手性农药通过生物制造实现大规模生产。

Abstract

Phosphinothricin (PPT) is one of the top three herbicides

known for its broad spectrum

high herbicidal activity

and non-selectivity

with a highly optimistic market prospect. However

PPT exists in two enantiomers (

-PPT and

-PPT)

with the herbicidal activity primarily stemming from

-PPT. Therefore

efficient synthesis of

-PPT with high optical purity is crucial. Pesticide manufacturing enterprises have attempted to develop chemical synthesis methods for

-PPT using approaches such as racemic compound splitting

asymmetric synthesis

natural amino acid chiral source method

and chiral auxiliary induction. However

due to challenges such as low stereo-selectivity

low product yield

and high production costs

large-scale production has not been achieved. Under the guidance of Academician Yin-Chu Shen

the “Father of Biopesticides in China”

our research group has conducted scientific research and industrial practice on the biosynthesis of

-PPT for over 20 years. In cooperation with multiple enterprises

we have developed more than ten process routes and technologies. Among them

five routes (racemic mixture derivatization-resolution route

racemic PPT-chiral separation route

generic compound cyanation followed by hydrolysis route

de novo

synthesis from common chemicals route

and synthesis of homoserine followed by chemical synthesis) are discussed in detail in this review. Each route’s reconstruction

establishment of bioinorganic amine technology

creation of biocatalysts

high-density fermentation for enzyme production

product separation and purification

and reaction equipment are included. Notably

we developed the BioHPP

a biomanufacturing technology for the synthesis of highly optically pure

-PPT. Based on this technology

a ten-thousand-ton digital and intelligent production line for

-PPT was established. Utilizing smart sensors and actuators

real-time data collection

transmission

analysis

and feedback adjustment were achieved at over a thousand control points. This led to fully automated parameter collection and control

increasing production efficiency by 50% and reducing labor intensity by more than 70%

thereby realizing the bio-intelligent manufacturing of ten thousand tons of

-PPT. Based on the long-term accumulation of our research efforts

we summarize and analyze the mainstream production processes of

-PPT

detailing on the principles and methods of biomanufacturing technology and synthetic biology to construct the key synthesis system for

-PPT. We also compare the characteristics and key points of industrialization implementation of these routes in terms of substrate synthesis and selection

types of biocatalysts

use of amino donors

and separation and purification. It can be foreseeable that

with the aid of synthetic biology technology

an increasing number of high-optical-purity chiral pesticides will be produced on a large scale through biomanufacturing in the future.

关键词

Keywords

references

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bThe National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals， Zhejiang University of Technology

aKey Laboratory of Bioorganic Synthesis of Zhejiang Province， College of Biotechnology and Bioengineering， Zhejiang University of Technology

The United Biotechnology （Zhuhai Hengqin） Co.， Ltd.

Zhuhai United Laboratories Co.， Ltd

School of Pharmaceutical Science，Sun Yat-Sen University

⁰

BioHPP®: a benchmark of biomanufacturing for high optically pure L-phosphinothricin

DOI：10.12211/2096-8280.2024-032

摘要

Abstract

关键词

Keywords

references

BioHPP^®: a benchmark of biomanufacturing for high optically pure L-phosphinothricin