Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae

Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined w...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-01, Vol.9 (1), p.647, Article 647
Main Authors: Nagy, Emma Zsófia Aletta, Nagy, Csaba Levente, Filip, Alina, Nagy, Katalin, Gál, Emese, Tőtős, Róbert, Poppe, László, Paizs, Csaba, Bencze, László Csaba
Format: Article
Language:English
Subjects:
Acids
Acrylic acid
Biocatalysts
Cinnamic acid
Computer applications
Decarboxylation
Ferulic acid
Flavin mononucleotide
Phenothiazine
Saccharomyces cerevisiae
Site-directed mutagenesis
Substrate specificity
Yeast
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553
cites cdi_FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553
container_end_page
container_issue 1
container_start_page 647
container_title Scientific reports
container_volume 9
creator Nagy, Emma Zsófia Aletta
Nagy, Csaba Levente
Filip, Alina
Nagy, Katalin
Gál, Emese
Tőtős, Róbert
Poppe, László
Paizs, Csaba
Bencze, László Csaba
description Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined with its high quality, atomic resolution structure nominates FDC1 an ideal candidate as flexible biocatalyst for decarboxylation reactions leading to synthetically valuable styrenes. Herein the substrate scope of ScFDC1 is explored on substituted cinnamic acids bearing different functional groups (-OCH , -CF or -Br) at all positions of the phenyl ring (o-, m-, p-) as well as on several biaryl and heteroaryl cinnamic acid analogues or derivatives with extended alkyl chain. It was found that E. coli whole cells expressing recombinant ScFDC1 could transform a large variety of substrates with high conversion, including several bulky aryl and heteroaryl cinnamic acid analogues, that characterize ScFDC1 as versatile and highly efficient biocatalyst. Computational studies revealed energetically favoured inactive binding positions and limited active site accessibility for bulky and non-linear substrates, such as 2-phenylthiazol-4-yl-, phenothiazine-2-yl- and 5-(4-bromophenyl)furan-2-yl) acrylic acids. In accordance with the computational predictions, site-directed mutagenesis of residue I330 provided variants with catalytic activity towards phenothiazine-2-yl acrylic acid and provides a basis for altering the substrate specificity of ScFDC1 by structure based rational design.
doi_str_mv 10.1038/s41598-018-36977-x
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6345843</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2344212126</sourcerecordid><originalsourceid>FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553</originalsourceid><addsrcrecordid>eNpVkU9PAjEQxRujEYN8AQ-miRc9rPbf7tKLiUFQExIP6rl221lYslBsdwl8e6sgwc6hL5mZ19f8ELqg5JYS3r8LgqaynxDaT3gm8zxZH6EzRkSaMM7Y8YHuoF4IMxJPyqSg8hR1OMlymUp2hj6H62XtfLWY4GYKOLRFaLxuojJuCdiVuATf1pXB2lQWWzDaF269qXUAfD16HNAbXHo3x2_amKmOamMgYAMeVlWoNJyjk1LXAXq7u4s-RsP3wXMyfn16GTyMEyOyvElKSS1QkwtZCEEkg0Lw0lhSxMBSWJvnWlrKU0qZ5QUvRUYsyYxhNAMq0pR30f3Wd9kWc7AGFvEftVr6aq79Rjldqf-dRTVVE7dSGRdpX_BocLUz8O6rhdComWv9ImZWjAvBaKwsTrHtlPEuBA_l_gVK1A8YtQWjIhj1C0at49LlYbb9yh8G_g2kRYpF</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2344212126</pqid></control><display><type>article</type><title>Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Nagy, Emma Zsófia Aletta ; Nagy, Csaba Levente ; Filip, Alina ; Nagy, Katalin ; Gál, Emese ; Tőtős, Róbert ; Poppe, László ; Paizs, Csaba ; Bencze, László Csaba</creator><creatorcontrib>Nagy, Emma Zsófia Aletta ; Nagy, Csaba Levente ; Filip, Alina ; Nagy, Katalin ; Gál, Emese ; Tőtős, Róbert ; Poppe, László ; Paizs, Csaba ; Bencze, László Csaba</creatorcontrib><description>Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined with its high quality, atomic resolution structure nominates FDC1 an ideal candidate as flexible biocatalyst for decarboxylation reactions leading to synthetically valuable styrenes. Herein the substrate scope of ScFDC1 is explored on substituted cinnamic acids bearing different functional groups (-OCH , -CF or -Br) at all positions of the phenyl ring (o-, m-, p-) as well as on several biaryl and heteroaryl cinnamic acid analogues or derivatives with extended alkyl chain. It was found that E. coli whole cells expressing recombinant ScFDC1 could transform a large variety of substrates with high conversion, including several bulky aryl and heteroaryl cinnamic acid analogues, that characterize ScFDC1 as versatile and highly efficient biocatalyst. Computational studies revealed energetically favoured inactive binding positions and limited active site accessibility for bulky and non-linear substrates, such as 2-phenylthiazol-4-yl-, phenothiazine-2-yl- and 5-(4-bromophenyl)furan-2-yl) acrylic acids. In accordance with the computational predictions, site-directed mutagenesis of residue I330 provided variants with catalytic activity towards phenothiazine-2-yl acrylic acid and provides a basis for altering the substrate specificity of ScFDC1 by structure based rational design.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-36977-x</identifier><identifier>PMID: 30679592</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Acids ; Acrylic acid ; Biocatalysts ; Cinnamic acid ; Computer applications ; Decarboxylation ; Ferulic acid ; Flavin mononucleotide ; Phenothiazine ; Saccharomyces cerevisiae ; Site-directed mutagenesis ; Substrate specificity ; Yeast</subject><ispartof>Scientific reports, 2019-01, Vol.9 (1), p.647, Article 647</ispartof><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553</citedby><cites>FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553</cites><orcidid>0000-0002-8358-1378</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2344212126/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2344212126?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,44625,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30679592$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nagy, Emma Zsófia Aletta</creatorcontrib><creatorcontrib>Nagy, Csaba Levente</creatorcontrib><creatorcontrib>Filip, Alina</creatorcontrib><creatorcontrib>Nagy, Katalin</creatorcontrib><creatorcontrib>Gál, Emese</creatorcontrib><creatorcontrib>Tőtős, Róbert</creatorcontrib><creatorcontrib>Poppe, László</creatorcontrib><creatorcontrib>Paizs, Csaba</creatorcontrib><creatorcontrib>Bencze, László Csaba</creatorcontrib><title>Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined with its high quality, atomic resolution structure nominates FDC1 an ideal candidate as flexible biocatalyst for decarboxylation reactions leading to synthetically valuable styrenes. Herein the substrate scope of ScFDC1 is explored on substituted cinnamic acids bearing different functional groups (-OCH , -CF or -Br) at all positions of the phenyl ring (o-, m-, p-) as well as on several biaryl and heteroaryl cinnamic acid analogues or derivatives with extended alkyl chain. It was found that E. coli whole cells expressing recombinant ScFDC1 could transform a large variety of substrates with high conversion, including several bulky aryl and heteroaryl cinnamic acid analogues, that characterize ScFDC1 as versatile and highly efficient biocatalyst. Computational studies revealed energetically favoured inactive binding positions and limited active site accessibility for bulky and non-linear substrates, such as 2-phenylthiazol-4-yl-, phenothiazine-2-yl- and 5-(4-bromophenyl)furan-2-yl) acrylic acids. In accordance with the computational predictions, site-directed mutagenesis of residue I330 provided variants with catalytic activity towards phenothiazine-2-yl acrylic acid and provides a basis for altering the substrate specificity of ScFDC1 by structure based rational design.</description><subject>Acids</subject><subject>Acrylic acid</subject><subject>Biocatalysts</subject><subject>Cinnamic acid</subject><subject>Computer applications</subject><subject>Decarboxylation</subject><subject>Ferulic acid</subject><subject>Flavin mononucleotide</subject><subject>Phenothiazine</subject><subject>Saccharomyces cerevisiae</subject><subject>Site-directed mutagenesis</subject><subject>Substrate specificity</subject><subject>Yeast</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpVkU9PAjEQxRujEYN8AQ-miRc9rPbf7tKLiUFQExIP6rl221lYslBsdwl8e6sgwc6hL5mZ19f8ELqg5JYS3r8LgqaynxDaT3gm8zxZH6EzRkSaMM7Y8YHuoF4IMxJPyqSg8hR1OMlymUp2hj6H62XtfLWY4GYKOLRFaLxuojJuCdiVuATf1pXB2lQWWzDaF269qXUAfD16HNAbXHo3x2_amKmOamMgYAMeVlWoNJyjk1LXAXq7u4s-RsP3wXMyfn16GTyMEyOyvElKSS1QkwtZCEEkg0Lw0lhSxMBSWJvnWlrKU0qZ5QUvRUYsyYxhNAMq0pR30f3Wd9kWc7AGFvEftVr6aq79Rjldqf-dRTVVE7dSGRdpX_BocLUz8O6rhdComWv9ImZWjAvBaKwsTrHtlPEuBA_l_gVK1A8YtQWjIhj1C0at49LlYbb9yh8G_g2kRYpF</recordid><startdate>20190124</startdate><enddate>20190124</enddate><creator>Nagy, Emma Zsófia Aletta</creator><creator>Nagy, Csaba Levente</creator><creator>Filip, Alina</creator><creator>Nagy, Katalin</creator><creator>Gál, Emese</creator><creator>Tőtős, Róbert</creator><creator>Poppe, László</creator><creator>Paizs, Csaba</creator><creator>Bencze, László Csaba</creator><general>Nature Publishing Group</general><general>Nature Publishing Group UK</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8358-1378</orcidid></search><sort><creationdate>20190124</creationdate><title>Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae</title><author>Nagy, Emma Zsófia Aletta ; Nagy, Csaba Levente ; Filip, Alina ; Nagy, Katalin ; Gál, Emese ; Tőtős, Róbert ; Poppe, László ; Paizs, Csaba ; Bencze, László Csaba</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acids</topic><topic>Acrylic acid</topic><topic>Biocatalysts</topic><topic>Cinnamic acid</topic><topic>Computer applications</topic><topic>Decarboxylation</topic><topic>Ferulic acid</topic><topic>Flavin mononucleotide</topic><topic>Phenothiazine</topic><topic>Saccharomyces cerevisiae</topic><topic>Site-directed mutagenesis</topic><topic>Substrate specificity</topic><topic>Yeast</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nagy, Emma Zsófia Aletta</creatorcontrib><creatorcontrib>Nagy, Csaba Levente</creatorcontrib><creatorcontrib>Filip, Alina</creatorcontrib><creatorcontrib>Nagy, Katalin</creatorcontrib><creatorcontrib>Gál, Emese</creatorcontrib><creatorcontrib>Tőtős, Róbert</creatorcontrib><creatorcontrib>Poppe, László</creatorcontrib><creatorcontrib>Paizs, Csaba</creatorcontrib><creatorcontrib>Bencze, László Csaba</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nagy, Emma Zsófia Aletta</au><au>Nagy, Csaba Levente</au><au>Filip, Alina</au><au>Nagy, Katalin</au><au>Gál, Emese</au><au>Tőtős, Róbert</au><au>Poppe, László</au><au>Paizs, Csaba</au><au>Bencze, László Csaba</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae</atitle><jtitle>Scientific reports</jtitle><addtitle>Sci Rep</addtitle><date>2019-01-24</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>647</spage><pages>647-</pages><artnum>647</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Ferulic acid decarboxylase from Saccharomyces cerevisiae (ScFDC1) was described to possess a novel, prenylated flavin mononucleotide cofactor (prFMN) providing the first enzymatic 1,3-dipolar cycloaddition mechanism. The high tolerance of the enzyme towards several non-natural substrates, combined with its high quality, atomic resolution structure nominates FDC1 an ideal candidate as flexible biocatalyst for decarboxylation reactions leading to synthetically valuable styrenes. Herein the substrate scope of ScFDC1 is explored on substituted cinnamic acids bearing different functional groups (-OCH , -CF or -Br) at all positions of the phenyl ring (o-, m-, p-) as well as on several biaryl and heteroaryl cinnamic acid analogues or derivatives with extended alkyl chain. It was found that E. coli whole cells expressing recombinant ScFDC1 could transform a large variety of substrates with high conversion, including several bulky aryl and heteroaryl cinnamic acid analogues, that characterize ScFDC1 as versatile and highly efficient biocatalyst. Computational studies revealed energetically favoured inactive binding positions and limited active site accessibility for bulky and non-linear substrates, such as 2-phenylthiazol-4-yl-, phenothiazine-2-yl- and 5-(4-bromophenyl)furan-2-yl) acrylic acids. In accordance with the computational predictions, site-directed mutagenesis of residue I330 provided variants with catalytic activity towards phenothiazine-2-yl acrylic acid and provides a basis for altering the substrate specificity of ScFDC1 by structure based rational design.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>30679592</pmid><doi>10.1038/s41598-018-36977-x</doi><orcidid>https://orcid.org/0000-0002-8358-1378</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 2045-2322
ispartof Scientific reports, 2019-01, Vol.9 (1), p.647, Article 647
issn 2045-2322
2045-2322
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6345843
source Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access
subjects Acids
Acrylic acid
Biocatalysts
Cinnamic acid
Computer applications
Decarboxylation
Ferulic acid
Flavin mononucleotide
Phenothiazine
Saccharomyces cerevisiae
Site-directed mutagenesis
Substrate specificity
Yeast
title Exploring the substrate scope of ferulic acid decarboxylase (FDC1) from Saccharomyces cerevisiae
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T09%3A57%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exploring%20the%20substrate%20scope%20of%20ferulic%20acid%20decarboxylase%20(FDC1)%20from%20Saccharomyces%20cerevisiae&rft.jtitle=Scientific%20reports&rft.au=Nagy,%20Emma%20Zs%C3%B3fia%20Aletta&rft.date=2019-01-24&rft.volume=9&rft.issue=1&rft.spage=647&rft.pages=647-&rft.artnum=647&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/s41598-018-36977-x&rft_dat=%3Cproquest_pubme%3E2344212126%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c467t-f91de1c749b44092eb43fcd0b41994dd77a9d135112d3b3f460d06cc216e14553%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2344212126&rft_id=info:pmid/30679592&rfr_iscdi=true