Screening of secondary metabolites biosynthesized with novel amino acid carrier protein system (970.3)

Abstract

LysW has been identified as a carrier protein in lysine biosynthetic pathway of hyperthermophilic bacteria Thermus thermophilus that protect the unstable intermediate and mediate latter step reactions efficiently. Recently it was revealed that LysW function as a carrier protein not only in lysine biosynthesis but also in arginine biosynthesis in hyperthermophilic archaeon, Sulfolobus acidcaldarius, suggesting that LysW is widely possessed by many species. We found the gene encoding LysW homolog in genome of many Actinomycetes. These Actinomycetes possess lysine and arginine biosynthetic pathway same as general bacteria, suggesting that lysW homolog is involved in secondary metabolism. In this study, we aimed to investigate the diversity of the biosynthetic machinery employing the carrier protein, and to discover a variety of novel compounds biosynthesized with this system. PCR screening revealed that 50 Actinomycetes strains out of 848 possess lysW homologs. Draft genome sequence analysis of 32 strains possessing lysW homologs revealed that various PKS and NRPS genes are encoded in the vicinity of lysW homologs, suggesting that lysW homologs are involved in biosynthesis of various secondary metabolites. The vicinity region of lysW homolog was cloned with cosmid vector and introduced into S. lividans TK23. The recombinant S. lividans TK23 produced a novel compound.