A novel erythromycin, 6-desmethyl erythromycin D, made by substituting an acyltransferase domain of the erythromycin polyketide synthase.
The acyltransferase (AT) domain in module 4 of the erythromycin polyketide synthase (PKS) was substituted with an AT domain from the rapamycin PKS module 2 in order to alter the substrate specificity from methylmalonyl-CoA to malonyl-CoA. The resulting strain produced 6-desmethyl erythromycin D as the predominant product. This AT domain swap completes the library of malonyl-CoA AT swaps on the erythromycin PKS and reinforces PKS engineering as a robust and generic tool.
Petkovic
Hrvoje
H
Biotica Technology Limited, 181 A Huntingdon Road, Cambridge CB3 0DJ, UK.
Lill
Rachel E
RE
Sheridan
Rose M
RM
Wilkinson
Barrie
B
McCormick
Ellen L
EL
McArthur
Hamish A I
HA
Staunton
James
J
Leadlay
Peter F
PF
Kendrew
Steven G
SG
D000217:Acyltransferases; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D004917:Erythromycin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D005285:Fermentation; D008826:Microbial Sensitivity Tests; D009097:Multienzyme Complexes; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000900:Anti-Bacterial Agents; D009097:Multienzyme Complexes; D004917:Erythromycin; D000217:Acyltransferases