Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2).

2.50
Hdl Handle:
http://hdl.handle.net/10033/582530
Title:
Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2).
Authors:
Yin, Jia; Hoffmann, Michael; Bian, Xiaoying; Tu, Qiang; Yan, Fu; Xia, Liqiu; Ding, Xuezhi; Stewart, A Francis; Müller, Rolf; Fu, Jun; Zhang, Youming
Abstract:
Linear plus linear homologous recombination-mediated recombineering (LLHR) is ideal for obtaining natural product biosynthetic gene clusters from pre-digested bacterial genomic DNA in one or two steps of recombineering. The natural product salinomycin has a potent and selective activity against cancer stem cells and is therefore a potential anti-cancer drug. Herein, we separately isolated three fragments of the salinomycin gene cluster (salO-orf18) from Streptomyces albus (S. albus) DSM41398 using LLHR and assembled them into intact gene cluster (106 kb) by Red/ET and expressed it in the heterologous host Streptomyces coelicolor (S. coelicolor) A3(2). We are the first to report a large genomic region from a Gram-positive strain has been cloned using LLHR. The successful reconstitution and heterologous expression of the salinomycin gene cluster offer an attractive system for studying the function of the individual genes and identifying novel and potential analogues of complex natural products in the recipient strain.
Affiliation:
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.
Citation:
Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2). 2015, 5:15081 Sci Rep
Journal:
Scientific reports
Issue Date:
2015
URI:
http://hdl.handle.net/10033/582530
DOI:
10.1038/srep15081
PubMed ID:
26459865
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS)

Full metadata record

DC FieldValue Language
dc.contributor.authorYin, Jiaen
dc.contributor.authorHoffmann, Michaelen
dc.contributor.authorBian, Xiaoyingen
dc.contributor.authorTu, Qiangen
dc.contributor.authorYan, Fuen
dc.contributor.authorXia, Liqiuen
dc.contributor.authorDing, Xuezhien
dc.contributor.authorStewart, A Francisen
dc.contributor.authorMüller, Rolfen
dc.contributor.authorFu, Junen
dc.contributor.authorZhang, Youmingen
dc.date.accessioned2015-11-23T15:32:44Zen
dc.date.available2015-11-23T15:32:44Zen
dc.date.issued2015en
dc.identifier.citationDirect cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2). 2015, 5:15081 Sci Repen
dc.identifier.issn2045-2322en
dc.identifier.pmid26459865en
dc.identifier.doi10.1038/srep15081en
dc.identifier.urihttp://hdl.handle.net/10033/582530en
dc.description.abstractLinear plus linear homologous recombination-mediated recombineering (LLHR) is ideal for obtaining natural product biosynthetic gene clusters from pre-digested bacterial genomic DNA in one or two steps of recombineering. The natural product salinomycin has a potent and selective activity against cancer stem cells and is therefore a potential anti-cancer drug. Herein, we separately isolated three fragments of the salinomycin gene cluster (salO-orf18) from Streptomyces albus (S. albus) DSM41398 using LLHR and assembled them into intact gene cluster (106 kb) by Red/ET and expressed it in the heterologous host Streptomyces coelicolor (S. coelicolor) A3(2). We are the first to report a large genomic region from a Gram-positive strain has been cloned using LLHR. The successful reconstitution and heterologous expression of the salinomycin gene cluster offer an attractive system for studying the function of the individual genes and identifying novel and potential analogues of complex natural products in the recipient strain.en
dc.language.isoenen
dc.titleDirect cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2).en
dc.typeArticleen
dc.contributor.departmentHelmholtz Institute for Pharmaceutical Research Saarland (HIPS);Saarland University, Building A4.1, 66123 Saarbruecken, Germany.en
dc.identifier.journalScientific reportsen
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