Abstract
Objective
To produce valerenic acid (VA) in Saccharomyces cerevisiae by engineering a heterologous synthetic pathway.
Result
Valerena-4,7(11)-diene synthase (VDS) derived from Valeriana officinalis (valerian) was expressed in S. cerevisiae to generate valerena-4,7(11)-diene as the precursor of VA. By overexpressing the key genes of the mevalonate pathway ERG8, ERG12 and ERG19, and integrating 4 copies of MBP (maltose-binding protein)-VDS-ERG20 gene expression caskets into the genome, the production of valerena-4,7(11)-diene was improved to 75 mg/L. On this basis, the cytochrome P450 monooxygenase LsGAO2 derived from Lactuca sativa was expressed to oxidize valerena-4,7(11)-diene to produce VA, and the most effective VA production strain was used for fermentation. The yield of VA reached 2.8 mg/L in the flask and 6.8 mg/L in a 5-L bioreactor fed glucose.
Conclusions
An S. cerevisiae strain was constructed and optimized to produce VA, but the valerena-4,7(11)-diene oxidation by LsGAO2 is still the rate-limiting step for VA synthesis that needs to be further optimized in future studies.
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This work was financially supported by the Key-Area Research and Development Program of Guangdong Province (Grant No. 2020B0303070002).
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Zhao, M., Zhang, C., Wang, H. et al. Biosynthesis of valerenic acid by engineered Saccharomyces cerevisiae. Biotechnol Lett 44, 857–865 (2022). https://doi.org/10.1007/s10529-022-03264-9
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DOI: https://doi.org/10.1007/s10529-022-03264-9