To supply enough amount of reveromycin A to continue in vivo experiments, we have conducted the studies required for improvement of reveromycin production. At first, S. reveromyceticus was cultured in 20 kinds of fermentation media and the metabolites were analyzed using a LC/MS equipped with a photodiode array. Several intermediates of reveromycin A have been isolated, and the fermentation condition of reveromycin A was determined. Next, the gene cluster required for reveromycin biosynthesis was cloned from S. reveromyceticus. The messenger RNA which was induced only at the reveromycin A production was prepared and cDNA encoding enoyl reductase was screened. Finally, a 90 kb DNA has been revealed as a gene cluster responsible for reveromycin A biosynthesis.
The integrated data of metabolomics and genomics enabled us to elucidate the biosynthesis route of reveromycin A.