Characterization of inthomycin biosynthetic gene cluster revealing new insights into carboxamide formation

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B ( 1 ) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the ¹⁵N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.