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The Oxidosqualene Cyclase from the Oomycete Saprolegnia parasitica Synthesizes Lanosterol as a Single Product
KTH, Skolan för bioteknologi (BIO), Glykovetenskap. Stockholm University, Sweden.
KTH, Skolan för bioteknologi (BIO), Glykovetenskap.ORCID-id: 0000-0003-1877-4154
KTH, Skolan för bioteknologi (BIO), Glykovetenskap. University of Adelaide, Australia.
KTH, Skolan för bioteknologi (BIO), Glykovetenskap. KTH, Skolan för kemivetenskap (CHE), Centra, Wallenberg Wood Science Center.ORCID-id: 0000-0002-3372-8773
2016 (Engelska)Ingår i: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 7, 1802Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Frontiers Media , 2016. Vol. 7, 1802
Nyckelord [en]
lanosterol biosynthesis, oomycete, Saprolegnia parasitica, oxidosqualene cyclase, sterols
Nationell ämneskategori
Mikrobiologi
Identifikatorer
URN: urn:nbn:se:kth:diva-198887DOI: 10.3389/fmicb.2016.01802ISI: 000388698600001Scopus ID: 2-s2.0-85006810293OAI: oai:DiVA.org:kth-198887DiVA: diva2:1061953
Forskningsfinansiär
Forskningsrådet Formas, 2013-1427
Anmärkning

QC 20170104

Tillgänglig från: 2017-01-04 Skapad: 2016-12-22 Senast uppdaterad: 2017-01-04Bibliografiskt granskad

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Dahlin, PaulSrivastava, VaibhavBulone, VincentMckee, Lauren S.
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GlykovetenskapWallenberg Wood Science Center
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