Advances in biosynthesis of L-arginine using engineered microorganisms

WANG Qian; GUO Shiting; XIN Bo; ZHONG Cheng; WANG Yu

doi:10.12211/2096-8280.2024-068

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Advances in biosynthesis of L-arginine using engineered microorganisms

Invited Review | 更新时间：2025-05-20

- Advances in biosynthesis of L-arginine using engineered microorganisms
- Synthetic Biology Journal Vol. 6, Issue 2, Pages: 290-305(2025)
- 作者机构：
  
  1.天津科技大学生物工程学院，天津 300222
  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
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2024-068
  CLC： Q816
- Received：28 August 2024，
  
  Revised：2024-10-31，
  
  Published：30 April 2025
- 稿件说明：
移动端阅览
王倩，果士婷，辛波，钟成，王钰. L-精氨酸的微生物合成研究进展［J］. 合成生物学， 2025， 6（2）： 290-305

WANG Qian， GUO Shiting， XIN Bo， ZHONG Cheng， WANG Yu. Advances in biosynthesis of L-arginine using engineered microorganisms［J］. Synthetic Biology Journal， 2025， 6（2）： 290-305
王倩，果士婷，辛波，钟成，王钰. L-精氨酸的微生物合成研究进展［J］. 合成生物学， 2025， 6（2）： 290-305 DOI： 10.12211/2096-8280.2024-068.

WANG Qian， GUO Shiting， XIN Bo， ZHONG Cheng， WANG Yu. Advances in biosynthesis of L-arginine using engineered microorganisms［J］. Synthetic Biology Journal， 2025， 6（2）： 290-305 DOI： 10.12211/2096-8280.2024-068.

摘要

L-精氨酸是一种碱性氨基酸，是护肤产品中常用的中和剂、保湿剂和抗氧化剂，此外，L-精氨酸还广泛应用于饲料、医药、食品等领域。以工程化的谷氨酸棒杆菌和大肠杆菌等微生物为催化剂，以可再生的淀粉糖为原料，通过微生物发酵的方法生产L-精氨酸是目前该产品最主要的生产方法。为创制高效的工程微生物菌种，早期研究者通常采用诱变筛选的方法，但由于突变的不确定性和非定向性，育种效率较低。随着合成生物技术的发展，人工设计L-精氨酸的合成途径和调控机制，并通过基因编辑理性创制工程微生物菌种成为研究的主流。本文综述了不同微生物中发现的L-精氨酸合成途径及调控机制，以谷氨酸棒杆菌和大肠杆菌为主，介绍了设计创制L-精氨酸高产菌种的合成生物学代谢改造策略，以及基于生物传感器的高通量筛选在L-精氨酸高产菌种筛选中的应用。最后，展望了进一步提高L-精氨酸生物合成水平的潜在策略，以及一碳原料等新型非粮碳资源在未来L-精氨酸生产中的应用前景。

Abstract

L-arginine is an alkaline amino acid that has been used as a neutralizer

moisturizer

and antioxidant in skin care products. In addition

L-arginine is also widely used in feed

medicine

and food industries. The wide range of applications for L-arginine has garnered significant attention for its robust production. L-arginine can be produced through protein hydrolysis and microbial fermentation. However

protein hydrolysis has drawbacks

including complicated operation

high purification cost

low recovery efficiency

and environmental pollution. In contrast

the microbial fermentation can use renewable and cheap feedstock. Besides

the process is performed under mild conditions

and thus is more environmentally friendly. At present

engineered microorganisms such as

Corynebacterium

glutamicum

and

Escherichia

coli

are major producers of L-arginine

and design and construction of microbial strains is the robust production of L-arginine through microbial fermentation. Random mutagenesis and screening strategies are used to develop L-arginine producing microbial strains

which are random with uncertainties

resulting in a low-efficiency for the breeding. With the development of synthetic biotechnology

development of L-arginine producing strains is empowered by the rational design of artificial synthetic pathways and regulatory machineries

taking advantages of advanced genome editing technologies. This paper reviews the progress in the studies of the synthetic pathways and regulatory mechanisms of L-arginine production that have been discovered in different microorganisms. Synthetic biology-guided metabolic engineering strategies for improving L-arginine production in

glutamicum

and

coli

are summarized. Besides

the application of the biosensor-based high-throughput sc

reening strategy for selecting L-arginine producing strains is introduced. Finally

potential strategies to enhancing L-arginine production and the possibility of using new carbon resources such as non-food biomass and one-carbon feedstock for L-arginine production are discussed. It is envisioned that synthetic biology-guided strain engineering will further enhance the production of L-arginine

particularly using non-food feedstock in the near future.

关键词

Keywords

references

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