Remodeling metabolism of Corynebacterium glutamicum for high-level dencichine production

Abstract

Dencichine, a sought-after compound in the medical industry, requires a more efficient and sustainable production method than the current plant extraction process. This study successfully remodeled the metabolic pathway of Corynebacterium glutamicum to produce dencichine from the precursors of L-2,3-diaminopropionate (L-DAP) and oxalyl-coenzyme A. Firstly, a synthetic pathway for L-DAP was established by introducing exogenous enzymes ZmaU/ZmaV. This resulted in a production of 628 mg/L by overexpressing key genes and reducing the endogenous competitive pathway. Secondly, an oxalyl-CoA synthetic pathway was created through the enzymatic conversion of glyoxylate by introducing heterologous enzymes. Finally, with the integration of the exogenous enzyme BAHD, de novo synthesis of dencichine in C. glutamicum was achieved, and production reached 31.75 mg/L within 48-hour fermentation. This achievement represents the first successful biosynthesis of dencichine in C. glutamicum, offering a promising approach for natural product through microbial fermentation.