Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite

Detalhes bibliográficos
Autor(a) principal: Braesel,Jana
Data de Publicação: 2019
Outros Autores: Eustáquio,Alessandra S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Journal of the Brazilian Chemical Society (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000300499
Resumo: Genome mining provides exciting opportunities for the discovery of natural products. However, in contrast to traditional bioassay-guided approaches, challenges of genome mining include poor or no expression of biosynthetic gene clusters (BGCs). Additionally, given that thousands of BGCs are now available through extensive genome sequencing, how does one select BGCs for discovery? Synthetic biology techniques can be used for BGC refactoring and activation, whereas resistance-gene-directed genome mining is a promising approach to discover bioactive natural products. Here we report the selection of a BGC by applying a resistance-gene-directed approach, cloning of the silent BGC from Micromonospora sp. B006, promoter exchange, and heterologous expression in Streptomyces coelicolor M1152. While we have yet to identify the encoded compound, we unexpectedly observed induction of a host metabolite, which we hypothesize is due to the presence of a caseinolytic protease C (ClpC) chaperone gene in the BGC, suggesting that ClpC chaperones may be used for BGC activation.
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spelling Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host MetaboliteClp proteaseClp ATPaseClp chaperonegenome mininggene activationnatural productantibioticGenome mining provides exciting opportunities for the discovery of natural products. However, in contrast to traditional bioassay-guided approaches, challenges of genome mining include poor or no expression of biosynthetic gene clusters (BGCs). Additionally, given that thousands of BGCs are now available through extensive genome sequencing, how does one select BGCs for discovery? Synthetic biology techniques can be used for BGC refactoring and activation, whereas resistance-gene-directed genome mining is a promising approach to discover bioactive natural products. Here we report the selection of a BGC by applying a resistance-gene-directed approach, cloning of the silent BGC from Micromonospora sp. B006, promoter exchange, and heterologous expression in Streptomyces coelicolor M1152. While we have yet to identify the encoded compound, we unexpectedly observed induction of a host metabolite, which we hypothesize is due to the presence of a caseinolytic protease C (ClpC) chaperone gene in the BGC, suggesting that ClpC chaperones may be used for BGC activation.Sociedade Brasileira de Química2019-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000300499Journal of the Brazilian Chemical Society v.30 n.3 2019reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20180234info:eu-repo/semantics/openAccessBraesel,JanaEustáquio,Alessandra S.eng2019-02-14T00:00:00Zoai:scielo:S0103-50532019000300499Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2019-02-14T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false
dc.title.none.fl_str_mv Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
title Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
spellingShingle Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
Braesel,Jana
Clp protease
Clp ATPase
Clp chaperone
genome mining
gene activation
natural product
antibiotic
title_short Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
title_full Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
title_fullStr Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
title_full_unstemmed Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
title_sort Heterologous Expression of a Putative ClpC Chaperone Gene Leads to Induction of a Host Metabolite
author Braesel,Jana
author_facet Braesel,Jana
Eustáquio,Alessandra S.
author_role author
author2 Eustáquio,Alessandra S.
author2_role author
dc.contributor.author.fl_str_mv Braesel,Jana
Eustáquio,Alessandra S.
dc.subject.por.fl_str_mv Clp protease
Clp ATPase
Clp chaperone
genome mining
gene activation
natural product
antibiotic
topic Clp protease
Clp ATPase
Clp chaperone
genome mining
gene activation
natural product
antibiotic
description Genome mining provides exciting opportunities for the discovery of natural products. However, in contrast to traditional bioassay-guided approaches, challenges of genome mining include poor or no expression of biosynthetic gene clusters (BGCs). Additionally, given that thousands of BGCs are now available through extensive genome sequencing, how does one select BGCs for discovery? Synthetic biology techniques can be used for BGC refactoring and activation, whereas resistance-gene-directed genome mining is a promising approach to discover bioactive natural products. Here we report the selection of a BGC by applying a resistance-gene-directed approach, cloning of the silent BGC from Micromonospora sp. B006, promoter exchange, and heterologous expression in Streptomyces coelicolor M1152. While we have yet to identify the encoded compound, we unexpectedly observed induction of a host metabolite, which we hypothesize is due to the presence of a caseinolytic protease C (ClpC) chaperone gene in the BGC, suggesting that ClpC chaperones may be used for BGC activation.
publishDate 2019
dc.date.none.fl_str_mv 2019-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000300499
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532019000300499
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.21577/0103-5053.20180234
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Química
publisher.none.fl_str_mv Sociedade Brasileira de Química
dc.source.none.fl_str_mv Journal of the Brazilian Chemical Society v.30 n.3 2019
reponame:Journal of the Brazilian Chemical Society (Online)
instname:Sociedade Brasileira de Química (SBQ)
instacron:SBQ
instname_str Sociedade Brasileira de Química (SBQ)
instacron_str SBQ
institution SBQ
reponame_str Journal of the Brazilian Chemical Society (Online)
collection Journal of the Brazilian Chemical Society (Online)
repository.name.fl_str_mv Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)
repository.mail.fl_str_mv ||office@jbcs.sbq.org.br
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