Activation of a plasmid situated type III PKS gene cluster by deletion of a wbl gene in deepsea derived Streptomyces somaliensis SCSIO ZH66
BackgroundActinomycete genome sequencing has disclosed a large number of cryptic secondary metabolite biosynthetic gene clusters. However, their unavailable or limited expression severely hampered the discovery of bioactive compounds. The whiB like (wbl) regulatory genes play important roles in morphological differentiation as well as secondary metabolism; and hence the wblAso gene was probed and set as the target to activate cryptic gene clusters in deepsea derived Streptomyces somaliensis SCSIO ZH66.ResultswblAso from deepsea derived S. somaliensis SCSIO ZH66 was inactivated, leading to significant changes of secondary metabolites production in the DwblAso mutant, from which a pyrone compound violapyrone B (VLP B) was isolated. Subsequently, the VLP biosynthetic gene cluster was identified and characterized, which consists of a type III polyketide synthase (PKS) gene vioA and a regulatory gene vioB; delightedly, inactivation of vioB led to isolation of another four VLPs analogues, among which one was new and two exhibited improved anti MRSA (methicillin resistant Staphylococcus aureus, MRSA) activity than VLP B. Moreover, transcriptional analysis revealed that the expression levels of whi genes (whiD, whiG, whiH and whiI) and wbl genes (wblC, wblE, wblH, wblI and wblK) were repressed by different degrees, suggesting an intertwined regulation mechanism of wblAso in morphological differentiation and secondary metabolism of S. somaliensis SCSIO ZH66.ConclusionswblA orthologues would be effective targets for activation of cryptic gene clusters in marine derived Streptomyces strains, notwithstanding the regulation mechanisms might be varied in different strains. Moreover, the availability of the vio gene cluster has enriched the diversity of type III PKSs, providing new opportunities to expand the chemical space of polyketides through biosynthetic engineering.
Microbial Cell Factories