Desertomycin D

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 γ-aminobutanoyl-CoA but with 4-guanidinylbutanoyl-CoA, to avoid facile cyclization of the starter unit. This hypothesis requires that there be a final-stage de-amidination of the corresponding guanidino-substituted natural product, but no enzyme for such a process 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 the 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 this proposed naturally evolved example of protective-group chemistry.

The non-polyenic macrocyclic antibiotic complex 1012 was isolated from the culture broth of a strain Streptomyces spectabilis 1. The complex was found to belong to the desertomycin complex. Three main compounds of complex 1012 were separated and purified by preparative chromatographic methods. The identification was performed by UV, IR, NMR and mass-spectrometric studies. It was proved that two of the compounds with MW. 1191, C61H109NO21 and MW. 1190, C61H106O22 were identical to desertomycin A and D. The other com-pound with MW.1028, C55H96O17 is new macrolactone, named deser-tomycin E. The structures were established by detailed spectroscopic analysis.