A novel amidinohydrolase provides the missing link in biosynthesis of amino-marginolactone antibiotics*

Abstract

Desertomycin A is an aminopolyol polyketide containing a macrolactone ring. We have proposed that desertomycin A and similar compounds (marginolactones) are formed by polyketide synthases primed not with gamma-aminobutanoyl-CoA but with 4- guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be final-stage de-amidination of the corresponding guanidino-substituted natural product, but no such enzyme has been described. We have now identified candidate amidinohydrolase genes within the desertomycin and primycin clusters. Deletion of the putative desertomycin amidinohydrolase gene dstH in Streptomyces macronensis led to accumulation of desertomycin B, the guanidino- form of the antibiotic. Also, purified DstH efficiently catalyzed the in vitro conversion of desertomycin B into the A form. Hence this amidinohydrolase furnishes the missing link in the proposal of a naturally-evolved example of protective group chemistry