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Structural characterization of CalO2: A putative orsellinic acid P450 oxidase in the calicheamicin biosynthetic pathway
Author(s) -
McCoy Jason G.,
Johnson Heather D.,
Singh Shanteri,
Bingman Craig A.,
Lei InKyoung,
Thorson Jon S.,
Phillips George N.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22131
Subject(s) - calicheamicin , polyketide , biosynthesis , polyketide synthase , docking (animal) , stereochemistry , adenylylation , biochemistry , oxidoreductase , active site , chemistry , natural product , enzyme , transferase , biology , medicine , nursing , myeloid leukemia , immunology
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 Å 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. Proteins 2009. © 2008 Wiley‐Liss, Inc.