Recent advances in the microbial production of L-arginine and its derivatives using engineering Corynebacterium...

L-arginine, a semi-essential alkaline amino acid, is widely utilized across industries such as food, feed, cosmetics, and pharmaceuticals. The primary industrial production strains for L-arginine are Corynebacterium glutamicum and Escherichia coli. The highest reported titers, yields, and productivities are 92.5 g/L, 0.40 g/g, 1.03 g/L/h, and 132 g/L, 0.51 g/g, 2.75 g/L/h, respectively. However, the development of efficient L-arginine-producing strains is constrained by several factors, including stringent feedback inhibition, lengthy biosynthetic pathways, high cofactor dependency, the accumulation of substantial by-products, high ammonia donor requirements, and limited product efflux capacity. This review provides an overview of the synthesis pathways and regulatory mechanisms underlying L-arginine production in C. glutamicum and E. coli, and summarizes metabolic engineering strategies for constructing efficient L-arginine cell factories. These strategies focus on enhancing core pathway carbon flux, improving precursor supply and product efflux, and optimizing cofactor and ammonia donor availability. The review concludes with a discussion of future directions, including enhancing cell stress tolerance, expanding substrate utilization, and developing cell factories for the production of L-arginine derivatives.