Review Article | Open Access

Volume 2025 |Article ID 100008 | https://doi.org/10.1016/j.bidere.2025.100008

Engineering Corynebacterium glutamicum cell factory for producing biochemicals

Kai Li ,^1,4 Meng-Lin Sun,^1,4 Bing Yuan,¹ Cheng Li,^2,3 Xin-Qing Zhao,¹ Chen-Guang Liu ,¹ Anthony J. Sinskey,^2,3 and Feng-Wu Bai¹

¹State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China
²Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
³Disruptive & Sustainable Technologies for Agricultural Precision, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore
⁴These authors have contributed equally to this work

Abstract

As an essential industrial microorganism, Corynebacterium glutamicum has been employed in amino acids production with a long history. Recent progress in its metabolic engineering has accelerated the establishment and optimization of this species as cell factories, making it another unique chassis. In this comprehensive review, we first highlight the progress made in the metabolic engineering of C. glutamicum to broaden its substrate spectrum, including sugars in lignocellulosic hydrolysate, cheap glycerol, and one-carbon compounds. Furthermore, we discuss the development of C. glutamicum as cell factories to produce various amino acids, with a focus on bulk, branched-chain and aromatic amino acids, organic acids such as succinic acid, lactic acid, and shikimic acid, and terpenoids. Finally, potential challenges faced by engineering C. glutamicum cell factories when using non-model feedstocks for biochemical production are discussed, focusing on stress tolerance, non-model substrate utilization, and the design of multifunctional cell factories, along with envisioned directions for future research.