L-cysteine

L-cysteine is a sulfur-containing proteinogenic amino acid [227]. It is a key precursor of biologically important molecules such as glutathione and contributes to multiple physiological processes, including immune modulation and the synthesis of structural proteins in hair and skin. In Escherichia coli, cysteine is synthesized from O-acetyl-L-serine through sulfur assimilation pathways that utilize sulfur sources such as sulfate or thiosulfate, while its degradation generates pyruvate, ammonium, and hydrogen sulfide [227].

In metabolic engineering, cysteine is an industrially valuable metabolite produced by microbial fermentation for applications in the agricultural, food, cosmetic, and pharmaceutical sectors [227]. Strategies to improve cysteine production in E. coli include enhancing sulfur conversion by overexpressing feedback-insensitive serine biosynthesis genes (serACB), serine acetyltransferase (cysE), and the transcriptional regulator cysB, while reducing metabolic losses through deletion of cysteine degradation genes such as yhaM and tnaA [227]. Additional improvements are achieved by overexpressing cysteine export systems (e.g., YdeD and YfiK), which decrease intracellular cysteine accumulation and alleviate toxicity [192, 365]. Beyond its role as a target product, cysteine can also be used as a process supplement to modulate enzyme regioselectivity, such as promoting indirubin production in recombinant E. coli expressing flavin-containing monooxygenase (FMO) [16]. However, elevated intracellular or extracellular cysteine concentrations inhibit E. coli growth, primarily through inhibition of threonine deaminase, highlighting the importance of balancing cysteine biosynthesis, export, and degradation during strain engineering [16].