Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin.

摘要: The post-polyketide synthase modification of geldanamycin (1) biosynthesis is interest as a means introducing structural diversity into the compound. From inactivation gene encoding carbamoyltransferase, we demonstrated that C-17 hydroxylation and C-21 oxidation precede O-carbamoylation hypothetical progeldanamycin does not possess double bond at C-4 C-5. More importantly, our result revealed new intermediates 4,5-dihydro-7-O-descarbamoyl-7-hydroxygeldanamycin (3) 4,5-dihydrogeldanamycin (5), indicating occurs prior to C-4,5 cis formation in biosynthesis.