Engineering thermotolerant Kluyveromyces marxianus strains for resveratrol production by simultaneous saccharification and fermentation of whole slurry corn cob

The microbial biosynthesis of the antioxidant compound resveratrol offers an eco-friendly and sustainable alternative to chemical synthesis or plant extraction. Here, we showed that Kluyveromyces marxianus strains produce p-coumaric acid, a key precursor of resveratrol, with higher titres achieved under increased agitation conditions. Through further strain engineering, resveratrol production was achieved using glucose, xylose, and/or ethanol as substrates. Xylose emerged as the most favourable carbon source for resveratrol production, with ethanol supplementation during xylose culture resulting in increased resveratrol titres by limiting the accumulation of the by-product xylitol. At 37 ◦C, resveratrol production from corn cob hydrolysate and whole slurry substantially increased the yield of resveratrol per sugar, reaching titres of up to 69.26 mg/L. This work shows, for the first time, resveratrol production by K. marxianus and from corn cob whole slurry, establishing foundations for the development of an integrated sustainable process for resveratrol production from lignocellulosic materials.