The post-polyketide synthase modification steps in the biosynthesis of the antitumor agent ansamitocin by Actinosynnema pretiosum.
The functions of six genes in the ansamitocin biosynthetic gene cluster of Actinosynnema pretiosum have been investigated by gene inactivation and chemical analysis of the mutants. They encode a halogenase (asm12), a carbamoyltransferase (asm21), a 20-O-methyltransferase (asm7), a 3-O-acyltransferase (asm19), an epoxidase (asm11), and an N-methyltransferase (asm10), respectively, and are responsible for the six post-PKS modification steps in ansamitocin formation. Several of the enzymes have relaxed substrate specificities, resulting in multiple parallel pathways in a metabolic grid, albeit with a preferred sequence of reactions as listed above.
Spiteller
Peter
P
Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700, USA.
Bai
Linquan
L
Shang
Guangdong
G
Carroll
Brian J
BJ
Yu
Tin-Wein
TW
Floss
Heinz G
HG
D000192:Actinomycetales / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D008453:Maytansine / Q000031:analogs & derivatives* / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D009097:Multienzyme Complexes; D008453:Maytansine; C015682:ansamitocins