(250f) Disrupting ABC Transporters to Promote Resveratrol Production in Saccharomyces Cerevisiae

Resveratrol as a nutritional polyphenol stilbenoid can be found in various plants including grapes, berries, peanuts, and other dietary sources. It is known as an antioxidant and demonstrates potentials in anti-glycation, anti-inflammation, anti-cancer, and anti-aging. This study focuses on enhancing the production of resveratrol, together with its hydrogenated form dihydro-resveratrol, in a previously engineered Saccharomyces cerevisiae strain by disrupting various endogenous transporters or genes. Eleven candidate genes proposed based on transcriptome analysis were disrupted individually, with the top three deficient mutants (*patent pending) yielding 94%, 72%, and 64% more resveratrol than the parent strain, respectively. Among the three, two encode plasma membrane ATP-binding cassette transporters reported to be involved in multidrug transportation. Two double-deficient mutants were subsequently constructed, resulting in higher titers (274.4 mg/L and 261.5 mg/L, respectively) through a five-day fermentation, which were nearly 3-fold and 2.8-fold higher than that of the initial parent strain, respectively. Our findings suggest the potential of increasing the production of resveratrol in manipulating transporters that are not obviously specific to the heterologous pathway.

*Patent pending: Strain genotypes will be provided in the conference talk. Please consult Zengyi Shao (zyshao@iastate.edu) before publishing the abstract on the conference website.