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The Oxidosqualene Cyclase from the Oomycete Saprolegnia parasitica Synthesizes Lanosterol as a Single Product
KTH, School of Biotechnology (BIO), Glycoscience. Stockholm University, Sweden.
KTH, School of Biotechnology (BIO), Glycoscience.
KTH, School of Biotechnology (BIO), Glycoscience. University of Adelaide, Australia.
KTH, School of Biotechnology (BIO), Glycoscience. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
2016 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 7, 1802Article in journal (Refereed) Published
Abstract [en]

The first committed step of sterol biosynthesis is the cyclisation of 2,3-oxidosqualene to form either lanosterol (LA) or cycloartenol (CA). This is catalyzed by an oxidosqualene cyclase (OSC). LA and CA are subsequently converted into various sterols by a series of enzyme reactions. The specificity of the OSC therefore determines the final composition of the end sterols of an organism. Despite the functional importance of OSCs, the determinants of their specificity are not well understood. In sterol-synthesizing oomycetes, recent bioinformatics, and metabolite analysis suggest that LA is produced. However, this catalytic activity has never been experimentally demonstrated. Here, we show that the OSC of the oomycete Saprolegnia parasitica, a severe pathogen of salmonid fish, has an uncommon sequence in a conserved motif important for specificity. We present phylogenetic analysis revealing that this sequence is common to sterol-synthesizing oomycetes, as well as some plants, and hypothesize as to the evolutionary origin of some microbial sequences. We also demonstrate for the first time that a recombinant form of the OSC from S. parasitica produces LA exclusively. Our data pave the way for a detailed structural characterization of the protein and the possible development of specific inhibitors of oomycete OSCs for disease control in aquaculture.

Place, publisher, year, edition, pages
Frontiers Media , 2016. Vol. 7, 1802
Keyword [en]
lanosterol biosynthesis, oomycete, Saprolegnia parasitica, oxidosqualene cyclase, sterols
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URN: urn:nbn:se:kth:diva-198887DOI: 10.3389/fmicb.2016.01802ISI: 000388698600001OAI: diva2:1061953
Swedish Research Council Formas, 2013-1427

QC 20170104

Available from: 2017-01-04 Created: 2016-12-22 Last updated: 2017-01-04Bibliographically approved

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Dahlin, PaulSrivastava, VaibhavBulone, VincentMckee, Lauren S.
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