Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120

Proceedings of the National Academy of Sciences of the United States of America
Claus SchneiderAlan R Brash

Abstract

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,...Continue Reading

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Citations

Sep 22, 2009·Phytochemistry·Alexandra Andreou, Ivo Feussner
Nov 14, 2008·Molecular Nutrition & Food Research·Claus Schneider
Oct 15, 2009·Protein Science : a Publication of the Protein Society·Svetlana PakhomovaMarcia E Newcomer
Apr 28, 2012·Biotechnology Advances·Young-Chul Joo, Deok-Kun Oh
Nov 23, 2017·Annual Review of Plant Biology·Claus Wasternack, Ivo Feussner
Sep 8, 2011·Angewandte Chemie·Sean M DeGuireGary A Sulikowski
Sep 10, 2008·Chembiochem : a European Journal of Chemical Biology·Claus Wasternack, Ivo Feussner
Dec 12, 2007·The Journal of Biological Chemistry·Yuxiang ZhengAlan R Brash
Apr 7, 2018·Science·Kai ChenFrances H Arnold
Mar 13, 2010·The Journal of Biological Chemistry·Alexandra AndreouIvo Feussner
Sep 23, 2016·Chembiochem : a European Journal of Chemical Biology·Zahra MashhadiAlan R Brash

Related Concepts

n-hexane, 3-(13)C-labeled cpd
Allene oxide synthase-lipoxygenase protein, Plexaura homomalla
9,10-epoxy-11-octadecenoic acid
9,10-epoxy-11,13,15-octadecatrienoic acid
9-hydroperoxylinolenic acid
Bacterial Proteins
Catalase T
High Pressure Liquid Chromatography Procedure
Epoxy Compounds
Hemeproteins

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