As natural metabolites, organic acids have been widely applied in food, pharmaceutical, and bio-based materials industries. Particularly, the short-chain organic acids, including C2, C3, C4, C5, and C6 organic acids, are necessary intermediate metabolites in cells and are also alternatives to some commercial chemical products. As the necessary metabolites in cells, most major short-chain organic acids can be produced through microbial fermentation. Specifically, with the development of synthetic biology, metabolic engineering could endow cells with the ability to produce more short-chain organic acid products including propionic acid, pyruvate, lactic acid, 3-hydroxypropionic acid, malic acid, succinic acid, fumaric acid, butyric acid, itaconic acid, α-ketoglutaric acid, glutaric acid, citric acid, gluconic acid, muconic acid, adipic acid, xylonic acid, and so on. The recent advances in the biological production of short-chain organic acids, as well as the challenges and perspectives, are summarized in this review to promote the generation of microbial cell factories for the production of short-chain organic acids.

Key points

• Outlines the production strategy of short-chain organic acids

• Provide guidance for efficient synthesis of short-chain organic acids

• Impacts the necessary factor of acid resistance on the successful production of host cells

作为天然代谢产物，有机酸已广泛应用于食品，制药和生物基材料行业。特别是，短链有机酸，包括C2，C3，C4，C5和C6有机酸，是细胞中必需的中间代谢产物，也是某些商业化学产品的替代品。作为细胞中必需的代谢产物，大多数主要的短链有机酸都可以通过微生物发酵产生。具体而言，随着合成生物学的发展，代谢工程可以赋予细胞产生更多短链有机酸产物的能力，包括丙酸，丙酮酸，乳酸，3-羟基丙酸，苹果酸，琥珀酸，富马酸，丁酸。酸，衣康酸，α-酮戊二酸，戊二酸，柠檬酸，葡萄糖酸，粘康酸，己二酸，木糖酸，等等。这篇综述总结了短链有机酸生物生产的最新进展，以及挑战和前景，以促进微生物细胞工厂的产生，以生产短链有机酸。

关键点

•概述了短链有机酸的生产策略

•为有效合成短链有机酸提供指导

•影响耐酸性的必要因素对宿主细胞成功生产的影响