Document Detail


Altering the regioselectivity of the subterminal fatty acid hydroxylase P450 BM-3 towards gamma- and delta-positions.
MedLine Citation:
PMID:  18984016     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytochrome P450 BM-3 monooxygenase from Bacillus megaterium (CYP102A1) catalyzes the subterminal hydroxylation of fatty acids with a chain length of 12-22 carbons. Wild-type P450 BM-3 oxidizes saturated fatty acids at subterminal positions producing a mixture of omega-1, omega-2 and omega-3 hydroxylated products. Using a rational site-directed mutagenesis approach, three new elements have been introduced into the substrate binding pocket of the monooxygenase, which greatly changed the product pattern of lauric acid hydroxylation. Particularly, substitutions at positions S72, V78 and I263 had an effect on the enzyme regioselectivity. The P450 BM-3 mutants V78A F87A I263G and S72Y V78A F87A were able to oxidize lauric acid not only at delta-position (14% and 16%, respectively), but also produced gamma- and beta-hydroxylated products. delta-Hydroxy lauric and gamma-hydroxy lauric acid are important synthons for the production of the corresponding lactones.
Authors:
Matthias Dietrich; Tuan Anh Do; Rolf D Schmid; Jürgen Pleiss; Vlada B Urlacher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-15
Journal Detail:
Title:  Journal of biotechnology     Volume:  139     ISSN:  0168-1656     ISO Abbreviation:  J. Biotechnol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-05-11     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8411927     Medline TA:  J Biotechnol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  115-7     Citation Subset:  IM    
Affiliation:
Institute of Technical Biochemistry, Universität Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
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MeSH Terms
Descriptor/Qualifier:
Bacterial Proteins / chemistry*,  genetics*,  metabolism
Binding Sites / genetics
Computer Simulation
Cytochrome P-450 Enzyme System / chemistry*,  genetics*,  metabolism
Lauric Acids / metabolism
Models, Molecular
Mutagenesis, Site-Directed*
NADPH-Ferrihemoprotein Reductase / chemistry*,  genetics*,  metabolism
Protein Conformation
Stereoisomerism
Substrate Specificity / genetics
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Lauric Acids; 143-07-7/lauric acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.6.2.4/NADPH-Ferrihemoprotein Reductase; EC 1.6.2.4/flavocytochrome P450 BM3 monoxygenases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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