Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin.
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.
Hong
Young-Soo
YS
Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Lee
Dongho
D
Kim
Woncheol
W
Jeong
Jae-Kap
JK
Kim
Chun-Gyu
CG
Sohng
Jae Kyung
JK
Lee
Jeong-Hyung
JH
Paik
Sang-Gi
SG
Lee
Jung Joon
JJ
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
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D048630:Polyketide Synthases; D019878:Carboxyl and Carbamoyl Transferases; C001277:geldanamycin