title: Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin.
abstract: 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.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Woncheol
authors.initials: W
authors.lastname: Kim
authors.forename: Jae-Kap
authors.initials: JK
authors.lastname: Jeong
authors.forename: Chun-Gyu
authors.initials: CG
authors.lastname: Kim
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
mesh_terms: D016227:Benzoquinones; D019878:Carboxyl and Carbamoyl Transferases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D047029:Lactams, Macrocyclic; D048630:Polyketide Synthases / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D048630:Polyketide Synthases; D019878:Carboxyl and Carbamoyl Transferases; C001277:geldanamycin