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

Autor: Hong YS; Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea., Lee D, Kim W, Jeong JK, Kim CG, Sohng JK, Lee JH, Paik SG, Lee JJ
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2004 Sep 15; Vol. 126 (36), pp. 11142-3.
DOI: 10.1021/ja047769m
Abstrakt: The post-polyketide synthase modification of geldanamycin (1) biosynthesis is of interest as a means of introducing structural diversity into the compound. From the inactivation of a gene encoding carbamoyltransferase, we demonstrated that the C-17 hydroxylation and the C-21 oxidation precede O-carbamoylation and that the hypothetical progeldanamycin does not possess a double bond at C-4 and C-5. More importantly, our result revealed new intermediates 4,5-dihydro-7-O-descarbamoyl-7-hydroxygeldanamycin (3) and 4,5-dihydrogeldanamycin (5), indicating that O-carbamoylation occurs prior to the C-4,5 cis double bond formation in geldanamycin biosynthesis.
Databáze: MEDLINE