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Structural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway.

TitleStructural characterization of CalO2: a putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway.
Publication TypeJournal Article
Year of Publication2009
AuthorsMcCoy JG, Johnson HD, Singh S, Bingman CA, Lei I-K, Thorson JS, Phillips GN
JournalProteins
Volume74
Issue1
Pagination50-60
Date Published2009 Jan
ISSN1097-0134
KeywordsAcyl Carrier Protein, Animals, Bacterial Proteins, Biosynthetic Pathways, Coenzyme A, Crystallography, X-Ray, Escherichia coli, Iodine, Ligands, Micromonospora, Oxidoreductases, Polyketide Synthases, Protein Binding, Protein Structure, Tertiary, Resorcinols, Streptomyces
Abstract

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.

DOI10.1002/prot.22131
Alternate JournalProteins
PubMed ID18561189
PubMed Central IDPMC2742692
Grant List5T32HG002760 / HG / NHGRI NIH HHS / United States
CA84374 / CA / NCI NIH HHS / United States
PSO GM64598 / GM / NIGMS NIH HHS / United States
R01 CA084374 / CA / NCI NIH HHS / United States
R01 CA084374-10 / CA / NCI NIH HHS / United States
T32-GM008505 / GM / NIGMS NIH HHS / United States
U19 CA113297 / CA / NCI NIH HHS / United States
Y1-CO-1020 / CO / NCI NIH HHS / United States
Y1-GM-1104 / GM / NIGMS NIH HHS / United States