Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis

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Published inJournal of Bacteriology Vol. 191; no. 10; pp. 3350 - 3358
Main Authors CHOI, Soo-Keun, PARK, Soo-Young, KIM, Rumi, KIM, Seong-Bin, LEE, Choong-Hwan, KIM, Jihyun F, PARK, Seung-Hwan
Format Journal Article
LanguageEnglish
Published Washington, DC American Society for Microbiology 01.05.2009
American Society for Microbiology (ASM)
Subjects
Antibiotics
Bacillus - enzymology
Bacillus - genetics
Bacillus subtilis
Bacillus subtilis - genetics
Bacillus subtilis - metabolism
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Biological and medical sciences
Chromatography, Liquid
Drug resistance
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation, Bacterial
Genetics and Molecular Biology
Genomics
Mass Spectrometry
Microbiology
Miscellaneous
Molecular Sequence Data
Multigene Family - genetics
Mutagenesis, Insertional
Open Reading Frames - genetics
Paenibacillus polymyxa
Peptides
Polymerase Chain Reaction
Polymyxins - metabolism
Proteins
Gene cluster
Bacillales
Microbiology
Paenibacillus polymyxa
Enzyme
Bacillus subtilis
Ligases
Bacteria
Identification
Bacillaceae
Gene expression
Online AccessGet full text

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Abstract Article Usage Stats Services JB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue JB About JB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0021-9193 Online ISSN: 1098-5530 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JB .asm.org, visit: JB       
AbstractList Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added L-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis.
Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA, pmxB, pmxC, pmxD, and pmxE. The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA, pmxB, and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added L-2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis. [PUBLICATION ABSTRACT]
Article Usage Stats Services JB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue JB About JB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy JB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0021-9193 Online ISSN: 1098-5530 Copyright © 2014 by the American Society for Microbiology.   For an alternate route to JB .asm.org, visit: JB       
Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the treatment of multidrug-resistant gram-negative pathogenic bacteria. Lack of information on the biosynthetic genes of polymyxin, however, has limited the study of structure-function relationships and the development of improved polymyxins. During whole genome sequencing of Paenibacillus polymyxa E681, a plant growth-promoting rhizobacterium, we identified a gene cluster encoding polymyxin synthetase. Here, we report the complete sequence of the gene cluster and its function in polymyxin biosynthesis. The gene cluster spanning the 40.6-kb region consists of five open reading frames, designated pmxA , pmxB , pmxC , pmxD , and pmxE . The pmxC and pmxD genes are similar to genes that encode transport proteins, while pmxA , pmxB , and pmxE encode polymyxin synthetases. The insertional disruption of pmxE led to a loss of the ability to produce polymyxin. Introduction of the pmx gene cluster into the amyE locus of the Bacillus subtilis chromosome resulted in the production of polymyxin in the presence of extracellularly added l -2,4-diaminobutyric acid. Taken together, our findings demonstrate that the pmx gene cluster is responsible for polymyxin biosynthesis.
Author Seung-Hwan Park
Seong-Bin Kim
Choong-Hwan Lee
Soo-Young Park
Jihyun F. Kim
Soo-Keun Choi
Rumi Kim
AuthorAffiliation Industrial Biotechnology & Bioenergy Research Center, KRIBB, Daejeon 305-806, Republic of Korea, 1 Institute of Hadong Green Tea, Hadong 667-805, Republic of Korea, 2 Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea 3
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Issue 10
Keywords Gene cluster
Bacillales
Microbiology
Paenibacillus polymyxa
Enzyme
Bacillus subtilis
Ligases
Bacteria
Identification
Bacillaceae
Gene expression
Language English
License CC BY 4.0
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Corresponding author. Mailing address: Industrial Biotechnology & Bioenergy Research Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea. Phone: 82-42-860-4410. Fax: 82-42-860-4488. E-mail: shpark@kribb.re.kr
These authors contributed equally to this study.
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Polymyxin, a long-known peptide antibiotic, has recently been reintroduced in clinical practice because it is sometimes the only available antibiotic for the...
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StartPage 3350
SubjectTerms Antibiotics
Bacillus - enzymology
Bacillus - genetics
Bacillus subtilis
Bacillus subtilis - genetics
Bacillus subtilis - metabolism
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Bacteriology
Biological and medical sciences
Chromatography, Liquid
Drug resistance
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation, Bacterial
Genetics and Molecular Biology
Genomics
Mass Spectrometry
Microbiology
Miscellaneous
Molecular Sequence Data
Multigene Family - genetics
Mutagenesis, Insertional
Open Reading Frames - genetics
Paenibacillus polymyxa
Peptides
Polymerase Chain Reaction
Polymyxins - metabolism
Proteins
Title Identification of a Polymyxin Synthetase Gene Cluster of Paenibacillus polymyxa and Heterologous Expression of the Gene in Bacillus subtilis
URI http://jb.asm.org/content/191/10/3350.abstract
https://www.ncbi.nlm.nih.gov/pubmed/19304848
https://www.proquest.com/docview/227076068
https://search.proquest.com/docview/21324530
https://pubmed.ncbi.nlm.nih.gov/PMC2687177
Volume 191
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