Structural characterization of CalO2: A putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic

Journal Article · Thu Aug 13 04:00:00 EDT 2009 · Proteins

DOI:https://doi.org/10.1002/prot.22131· OSTI ID:1005691

McCoy, Jason G; Johnson, Heather D; Singh, Shanteri; Bingman, Craig A; Lei, In-Kyoung; Thorson, Jon S

Although bacterial iterative Type I polyketide synthases are now known to participate in the biosynthesis of a small set of diverse natural products, the subsequent downstream modification of the resulting polyketide products remains poorly understood. Toward this goal, we report the X-ray structure determination at 2.5 A resolution and preliminary characterization of the putative orsellenic acid P450 oxidase (CalO2) involved in calicheamicin biosynthesis. These studies represent the first crystal structure for a P450 involved in modifying a bacterial iterative Type I polyketide product and suggest the CalO2-catalyzed step may occur after CalO3-catalyzed iodination and may also require a coenzyme A- (CoA) or acyl carrier protein- (ACP) bound substrate. Docking studies also reveal a putative docking site within CalO2 for the CLM orsellinic acid synthase (CalO5) ACP domain which involves a well-ordered helix along the CalO2 active site cavity that is unique compared with other P450 structures.

• Research Organization: Argonne National Laboratory (ANL)
• Sponsoring Organization: USDOE
• OSTI ID: 1005691
• Journal Information: Proteins, Journal Name: Proteins Journal Issue: (1) ; 01, 2009 Vol. 74; ISSN PSFGEY; ISSN 0887-3585
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
BIOSYNTHESIS
CARRIERS
COENZYMES
CRYSTAL STRUCTURE
IODINATION
MODIFICATIONS
OXIDASES
RESOLUTION