Heterogenous biosynthesis of medicarpin using engineered Saccharomyces cerevisiae

Abstract

Abstract Background Medicarpin is one important bioactive compound with multiple medicinal activities, including anti-tumor, anti-osteoporosis, anti-bacterial effects. Medicarpin is assigned to pterocarpans derived from medicinal plants, such as Sophora japonica, Glycyrrhiza uralensisFisch. and Glycyrrhiza glabra L.However, these medicinal plants only contain low amounts of medicarpin. Moreover, the planting area for medicarpin-producing plants is limited, thus, current medicarpin supply cannot satisfy the great demands of medicinal markets. Results In this study, eight key genes involved in medicarpin biosynthesis were identified by comparative transcriptome analysis and bioinformatic analyses. In vitro and in vivoenzymatic activities assays confirmed the catalytic functions of candidate enzymes were responsible for the biosynthesis of medicarpin and medicarpin intermediates. Further engineering of these genes in Saccharomyces cerevisiae achieved the heterogenous biosynthesis of medicarpin using liquiritigenin as the substrate, and the final medicarpin titer was 0.82 ± 0.18 mg/L. By increasing the gene copy number of VRand PTS, the final titer of the medicarpin increased to 2.05 ± 0.72 mg/L. Conclusion This study provides a solid foundation for the economical and sustainable production of medicarpin by synthetic biology strategy.