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

Yong-Jiang WANG,Li WANG,Xin HE,Dong-Dong XU,Jun TANG,Ya-Tuan MA,Yi-Jun YAN,Yu-Cheng GU,Jing YANG,Sheng-Xiong HUANG

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 15 N -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.