ABSTRACT

Gastrodin is a plant-derived natural compound with neuroprotective and anticancer properties, commercially produced by solvent extraction from Gastrodia elata. Microbial fermentation offers a more economical and environmentally friendly alternative for gastrodin production. However, the productivity of engineered platforms using glucose remains limited, posing a key challenge for industrial application. This study aimed at engineering Corynebacterium glutamicum for gastrodin production from glucose. First, the gene pobA was deleted in C. glutamicum ATCC13032 and the gene ubiC from Escherichia coli encoding the chorismate-pyruvate lyase was overexpressed, the resulting strain WN01/pB1 could accumulate 4-hydroxybenzoic acid, one of the key precursors for gastrodin biosynthesis. Next, the gene car from Mycobacterium abscessus encoding the carboxylic acid reductase and the gene AtUGT from Arabidopsis thaliana encoding the UDP-glucosyltransferase were overexpressed in WN02, together with the gene ubiC from E. coli, and the resulting strain WN02/pB6 could produce 3.67 g/L gastrodin. Then, the 4-hydroxybenzyl alcohol biosynthesis pathway was improved, the heterologous gene expression was modified, the initial glucose concentration was optimized, and the gastrodin production in WN05/pB6 reached 7.37 g/L. After 72 h fed-batch fermentation in a 5 L fermenter, the final strain WN05/pB6 could produce 17.77 g/L gastrodin with a productivity of 0.246 g/L/h. This study provides a novel strategy for the efficient production of gastrodin and demonstrates that C. glutamicum is a viable chassis for gastrodin production.