Document Detail

Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120.
MedLine Citation:
PMID:  18025466     Owner:  NLM     Status:  MEDLINE    
Biological transformations of polyunsaturated fatty acids often lead to chemically unstable products, such as the prostaglandin endoperoxides and leukotriene A(4) epoxide of mammalian biology and the allene epoxides of plants. Here, we report on the enzymatic production of a fatty acid containing a highly strained bicyclic four-carbon ring, a moiety known previously only as a model compound for mechanistic studies in chemistry. Starting from linolenic acid (C18.3omega3), a dual function protein from the cyanobacterium Anabaena PCC 7120 forms 9R-hydroperoxy-C18.3omega3 in a lipoxygenase domain, then a catalase-related domain converts the 9R-hydroperoxide to two unstable allylic epoxides. We isolated and identified the major product as 9R,10R-epoxy-11trans-C18.1 containing a bicyclo[1.1.0]butyl ring on carbons 13-16, and the minor product as 9R,10R-epoxy-11trans,13trans,15cis-C18.omega3, an epoxide of the leukotriene A type. Synthesis of both epoxides can be understood by initial transformation of the hydroperoxide to an epoxy allylic carbocation. Rearrangement to an intermediate bicyclobutonium ion followed by deprotonation gives the bicyclobutane fatty acid. This enzymatic reaction has no parallel in aqueous or organic solvent, where ring-opened cyclopropanes, cyclobutanes, and homoallyl products are formed. Given the capability shown here for enzymatic formation of the highly strained and unstable bicyclobutane, our findings suggest that other transformations involving carbocation rearrangement, in both chemistry and biology, should be examined for the production of the high energy bicyclobutanes.
Claus Schneider; Katrin Niisuke; William E Boeglin; Markus Voehler; Donald F Stec; Ned A Porter; Alan R Brash
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-11-19
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  104     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-11-29     Completed Date:  2008-01-15     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  18941-5     Citation Subset:  IM    
Department of Pharmacology, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
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MeSH Terms
Anabaena / enzymology*,  genetics
Bacterial Proteins / chemistry,  genetics,  metabolism*
Catalase / chemistry
Chromatography, High Pressure Liquid
Conserved Sequence
Epoxy Compounds
Hemeproteins / chemistry,  genetics,  metabolism*
Leukotriene A4 / analogs & derivatives
Linoleic Acids / biosynthesis*
Linolenic Acids / metabolism
Lipoxygenase / chemistry,  genetics,  metabolism*
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Oleic Acids / biosynthesis*
Peptide Fragments / genetics,  metabolism
Peroxidases / chemistry
Protein Structure, Tertiary
Recombinant Proteins / metabolism
Sequence Homology, Amino Acid
Spectrophotometry, Ultraviolet
Grant Support
Reg. No./Substance:
0/9,10-epoxy-11,13,15-octadecatrienoic acid; 0/9,10-epoxy-11-octadecenoic acid; 0/9-hydroperoxylinolenic acid; 0/Bacterial Proteins; 0/Epoxy Compounds; 0/Hemeproteins; 0/Hexanes; 0/Leukotriene A4; 0/Linoleic Acids; 0/Linolenic Acids; 0/Oleic Acids; 0/Peptide Fragments; 0/Recombinant Proteins; 2DDG612ED8/n-hexane; EC 1.11.1.-/Peroxidases; EC; EC; EC oxide synthase-lipoxygenase protein, Plexaura homomalla

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

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