Engineering aminoacyl-tRNA synthetase activity to enhance branched-chain amino acid biosynthesis

IF 3.4 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie Pub Date : 2026-07-01 Epub Date: 2026-03-31 DOI:10.1016/j.biochi.2026.03.014

Alice S. Derunets, Alexander S. Yanenko

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Abstract

Branched-chain amino acids (BCAA; valine, leucine, and isoleucine) are high-value metabolites. Its microbial production can be significantly increased by metabolic engineering. While pathway engineering dominates current efforts, the BCAA-specific aminoacyl-tRNA synthetases (aaRS) represent a powerful but overlooked lever. They not only charge tRNAs for accurate translation but also influence cellular BCAA availability. Disrupting aaRS activity or tRNA charging increases (p)ppGpp levels, which activates BCAA biosynthesis by means of the stringent response and attenuation control. Recent research has begun to harness this link by engineering aaRS–tRNA pairs to create growth-coupled selection systems, which have successfully increased amino acid titers in Escherichia coli and Corynebacterium glutamicum. Yet, direct engineering of BCAA aaRS remains rare. Integrating tRNA modifications, targeted aaRS mutagenesis, and synthetic biology tools offers a compelling route to engineer superior microbial cell factories for industrial-scale BCAA production.

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改造氨基酰基- trna合成酶活性，促进支链氨基酸的生物合成

支链氨基酸（BCAA、缬氨酸、亮氨酸和异亮氨酸）是高价值的代谢物。通过代谢工程可以显著提高其微生物产量。虽然途径工程在目前的研究中占主导地位，但bcaa特异性氨基酰基- trna合成酶（aaRS）是一个强大但被忽视的杠杆。它们不仅为准确翻译trna而收费，而且还影响细胞BCAA的可用性。破坏aaRS活性或tRNA充电增加ppGpp水平，通过严格的响应和衰减控制激活BCAA生物合成。最近的研究已经开始利用这种联系，通过工程aaRS-tRNA对来创建生长偶联选择系统，该系统已经成功地提高了大肠杆菌和谷氨酸棒状杆菌的氨基酸滴度。然而，直接工程的BCAA aaRS仍然很少。整合tRNA修饰、靶向aaRS诱变和合成生物学工具，为设计用于工业规模BCAA生产的优质微生物细胞工厂提供了一条引人注目的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimie 生物-生化与分子生物学

CiteScore

7.20

自引率

2.60%

发文量

219

审稿时长

40 days

期刊介绍： Biochimie publishes original research articles, short communications, review articles, graphical reviews, mini-reviews, and hypotheses in the broad areas of biology, including biochemistry, enzymology, molecular and cell biology, metabolic regulation, genetics, immunology, microbiology, structural biology, genomics, proteomics, and molecular mechanisms of disease. Biochimie publishes exclusively in English. Articles are subject to peer review, and must satisfy the requirements of originality, high scientific integrity and general interest to a broad range of readers. Submissions that are judged to be of sound scientific and technical quality but do not fully satisfy the requirements for publication in Biochimie may benefit from a transfer service to a more suitable journal within the same subject area.