화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.140, No.51, 18009-18015, 2018
Design and Biosynthesis of Dimeric Alboflavusins with Biaryl Linkages via Regiospecific C-C Bond Coupling
Alboflavusins (AFNs) are a group of cyclo-hexapeptides with moderate antibacterial and antitumor activities from Streptomyces alboflavus sp. 313. In vivo and in vitro studies proposed that AFNs are biosynthesized by a nonribosomal peptide synthetase machinery, and the 6-Cl-L-Trp precursor is supplied by a tryptophan halogenase gene located outside the afn gene cluster. Guided by the structure-activity relationship knowledge about the AFN-like cyclo-hexapeptides, two dimeric AFNs (di-AFNs) with regiospecific biaryl linkages were designed and generated biotechnologically by expressing the P450 gene hmtS or clpS in S. alboflavus wild-type and mutant strains. The di-AFNs displayed much better antibacterial and antitumor activities than their monomers as anticipated, exemplifying a rational strategy to generate natural product congeners with improved bioactivities.