Genome-based analysis of non-ribosomal peptide synthetase and type-I polyketide synthase gene clusters in all type strains of the genus Herbidospora

Hisayuki Komaki, Natsuko Ichikawa, Akio Oguchi, Moriyuki Hamada, Tomohiko Tamura, Nobuyuki Fujita

The genus Herbidospora comprises actinomycetes belonging to the family Streptosporangiaceae and currently contains five recognized species. Although other genera of this family often produce bioactive secondary metabolites, Herbidospora strains have not yet been reported to produce secondary metabolites. In the present study, to assess their potential as secondary metabolite producers, we sequenced the whole genomes of the five type strains and searched for the presence of their non-ribosomal peptide synthetase (NRPS) and type-I polyketide synthase (PKS) gene clusters. These clusters are involved in the major secondary metabolite-synthetic pathways in actinomycetes. The genome sizes of Herbidospora cretacea NBRC 15474(T), Herbidospora mongoliensis NBRC 105882(T), Herbidospora yilanensis NBRC 106371(T), Herbidospora daliensis NBRC 106372(T) and Herbidospora sakaeratensis NBRC 102641(T) were 8.3, 9.0, 7.9, 8.5 and 8.6 Mb, respectively. They contained 15-18 modular NRPS and PKS gene clusters. Thirty-two NRPS and PKS pathways were identified, among which 9 pathways were conserved in all 5 strains, 8 were shared in 2-4 strains, and the remaining 15 were strain-specific. We predicted the chemical backbone structures of non-ribosomal peptides and polyketides synthesized by these gene clusters, based on module number and domain organization of NRPSs and PKSs. The relationship between 16S rRNA gene sequence-based phylogeny of the five strains and the distribution of their NRPS and PKS gene clusters were also discussed. The genomes of Herbidospora strains carry as many NRPS and PKS gene clusters, whose products are yet to be isolated, as those of Streptomyces. Herbidospora members should synthesize large and diverse metabolites, many of whose chemical structures are yet to be reported. In addition to those conserved within this genus, each strain possesses many strain-specific gene clusters, suggesting the diversity of these pathways. This diversity could be accounted for by genus-level vertical inheritance and recent acquisition of these gene clusters during evolution. This genome analysis suggested that Herbidospora strains are an untapped and attractive source of novel secondary metabolites.