Balancing Redox Homeostasis to Improve <scp>l</scp>-Cysteine Production in <i>Corynebacterium glutamicum</i>
Huanmin Du, Yuting Qi, Jinfang Qiao, Lingcong Li, Ning Xu, Li Shao, Liang Wei, Jun Liu
Abstract
l -Cysteine is a valuable sulfur-containing amino acid with applications across a wide range of fields. Recently, microbial fermentation has emerged as a method to produce l -cysteine. However, cellular redox stress from high levels of l -cysteine is a bottleneck for achieving efficient production. In this study, we aimed to facilitate l -cysteine biosynthesis by modulating cellular redox homeostasis through the introduction of the natural antioxidant astaxanthin in Corynebacterium glutamicum . To achieve this, we first introduced an exogenous astaxanthin synthesis module in C. glutamicum . Then, an l -cysteine-dependent autonomous bifunctional genetic switch was developed to dynamically regulate the l -cysteine and astaxanthin biosynthesis pathway to maintain cellular redox homeostasis. This regulation system achieved high biosynthesis of astaxanthin, which significantly facilitated l -cysteine production. Finally, engineered strain Cg-10 produced 8.45 g/L l -cysteine and 95 mg/L astaxanthin in a 5 L bioreactor, both of which are the highest reported levels in C. glutamicum .