7-O-descarbamoyl-7-hydroxygeldanamycin, a minor component from the gdmN disruption mutant of Streptomyces hygroscopicus 17997

The Journal of Antibiotics
2010.0

Abstract

To examine whether there are other undiscovered geldanamycin (GDM) analogs in the gdmN disruption mutant of Streptomyces hygroscopicus 17997, a time-course monitoring of its fermentation culture was conducted. The fermentation supernatants were extracted with ethyl acetate, and a novel GDM analog was isolated via silica-gel TLC, HPLC, liquid chromatography-ESI(+)-MS and NMR analyses. The analog was identified as 7-O-descarbamoyl-7-hydroxygeldanamycin (designated CT-1-7x), which is the C-4,5 olefinic form of 4,5-dihydro-7-O-descarbamoyl-7-hydroxygeldanamycin (CT-1-7). Bioconversion experiments showed that CT-1-7x failed to be converted to GDM by GDM-pks- (a GDM PKS gene disruption mutant retaining post-PKS tailoring genes), whereas CT-1-7 could be converted to GDM. This indicates that the carbamoyltransferase in GDM biosynthesis exhibits substrate specificity for the C-4,5 single bond, and 7-O-carbamoylation must occur before C-4,5 oxidation in the post-polyketide synthase (PKS) tailoring process of GDM biosynthesis.

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