Substrate recognition and channeling of monomodules from the pikromycin polyketide synthase.
The unique ability of the pikromycin (Pik) polyketide synthase to generate 12- and 14-membered ring macrolactones presents an opportunity to explore the fundamental processes underlying polyketide synthesis, specifically the mechanistic details of the chain extension process. We have overexpressed and purified PikAIII (module 5) and PikAIV (module 6) and assessed the ability of these proteins to generate tri- and tetraketide lactone products using N-acetylcysteamine-activated diketides and (14)C-methylmalonyl-CoA as substrates. Comparison of the stereochemical specificities for PikAIII and PikAIV and the reported values for the DEBS modules reveals significant differences between these systems.
Beck
Brian J
BJ
Department of Microbiology and Biotechnology Institute, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Aldrich
Courtney C
CC
Fecik
Robert A
RA
Reynolds
Kevin A
KA
Sherman
David H
DH
D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D018942:Macrolides / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology
D018942:Macrolides; D009097:Multienzyme Complexes; C003145:picromycin