Preparation of erythromycin analogs having functional groups at C-15.
Chemobiosynthesis has been used to prepare analogs of erythromycins having unique functional groups at the 15-position. Using diketide thioester feeding to genetically engineered Streptomyces coelicolor, analogs of 6-deoxyerythronolide B were prepared having 15-fluoro, 15-chloro, and 15-azido groups. Bioconversion using a genetically engineered mutant of Saccharopolyspora erythraea was used to produce 15-fluoroerythromycin A and 15-azidoerythromycin A. These new erythromycin analogs provide antibacterial macrolides with unique physicochemical properties and functional groups that allow for selective derivatization.
Ashley
Gary W
GW
Kosan Biosciences, Inc., 3832, Bay Center Place, Hayward, California 94545, USA. Ashley@kosan.com
Burlingame
Mark
M
Desai
Ruchir
R
Fu
Hong
H
Leaf
Tim
T
Licari
Peter J
PJ
Tran
Chau
C
Abbanat
Darren
D
Bush
Karen
K
Macielag
Mark
M
D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000737:chemistry; D005818:Genetic Engineering; D015394:Molecular Structure; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism
C514531:15-azidoerythromycin A; C514530:15-fluoroerythromycin A; D004917:Erythromycin