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The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin

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The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin. / Gerc, Amy J; Song, Lijiang; Challis, Gregory L; Stanley-Wall, Nicola R; Coulthurst, Sarah J.

In: PLoS ONE, Vol. 7, No. 9, 2012, p. e44673.

Research output: Contribution to journalArticle

Harvard

Gerc, AJ, Song, L, Challis, GL, Stanley-Wall, NR & Coulthurst, SJ 2012, 'The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin' PLoS ONE, vol 7, no. 9, pp. e44673., 10.1371/journal.pone.0044673

APA

Gerc, A. J., Song, L., Challis, G. L., Stanley-Wall, N. R., & Coulthurst, S. J. (2012). The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin. PLoS ONE, 7(9), e44673. 10.1371/journal.pone.0044673

Vancouver

Gerc AJ, Song L, Challis GL, Stanley-Wall NR, Coulthurst SJ. The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin. PLoS ONE. 2012;7(9):e44673. Available from: 10.1371/journal.pone.0044673

Author

Gerc, Amy J; Song, Lijiang; Challis, Gregory L; Stanley-Wall, Nicola R; Coulthurst, Sarah J / The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin.

In: PLoS ONE, Vol. 7, No. 9, 2012, p. e44673.

Research output: Contribution to journalArticle

Bibtex - Download

@article{4e412907e4c64c4a971fc4da6a732bfa,
title = "The Insect Pathogen Serratia marcescens Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin",
author = "Gerc, {Amy J} and Lijiang Song and Challis, {Gregory L} and Stanley-Wall, {Nicola R} and Coulthurst, {Sarah J}",
year = "2012",
doi = "10.1371/journal.pone.0044673",
volume = "7",
number = "9",
pages = "e44673",
journal = "PLoS ONE",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - The Insect Pathogen<em> Serratia marcescens </em>Db10 Uses a Hybrid Non-Ribosomal Peptide Synthetase-Polyketide Synthase to Produce the Antibiotic Althiomycin

A1 - Gerc,Amy J

A1 - Song,Lijiang

A1 - Challis,Gregory L

A1 - Stanley-Wall,Nicola R

A1 - Coulthurst,Sarah J

AU - Gerc,Amy J

AU - Song,Lijiang

AU - Challis,Gregory L

AU - Stanley-Wall,Nicola R

AU - Coulthurst,Sarah J

PY - 2012

Y1 - 2012

N2 - There is a continuing need to discover new bioactive natural products, such as antibiotics, in genetically-amenable micro-organisms. We observed that the enteric insect pathogen, Serratia marcescens Db10, produced a diffusible compound that inhibited the growth of Bacillis subtilis and Staphyloccocus aureus. Mapping the genetic locus required for this activity revealed a putative natural product biosynthetic gene cluster, further defined to a six-gene operon named alb1-alb6. Bioinformatic analysis of the proteins encoded by alb1-6 predicted a hybrid non-ribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line (Alb4/5/6), tailoring enzymes (Alb2/3) and an export/resistance protein (Alb1), and suggested that the machinery assembled althiomycin or a related molecule. Althiomycin is a ribosome-inhibiting antibiotic whose biosynthetic machinery had been elusive for decades. Chromatographic and spectroscopic analyses confirmed that wild type S. marcescens produced althiomycin and that production was eliminated on disruption of the alb gene cluster. Construction of mutants with in-frame deletions of specific alb genes demonstrated that Alb2-Alb5 were essential for althiomycin production, whereas Alb6 was required for maximal production of the antibiotic. A phosphopantetheinyl transferase enzyme required for althiomycin biosynthesis was also identified. Expression of Alb1, a predicted major facilitator superfamily efflux pump, conferred althiomycin resistance on another, sensitive, strain of S. marcescens. This is the first report of althiomycin production outside of the Myxobacteria or Streptomyces and paves the way for future exploitation of the biosynthetic machinery, since S. marcescens represents a convenient and tractable producing organism.

AB - There is a continuing need to discover new bioactive natural products, such as antibiotics, in genetically-amenable micro-organisms. We observed that the enteric insect pathogen, Serratia marcescens Db10, produced a diffusible compound that inhibited the growth of Bacillis subtilis and Staphyloccocus aureus. Mapping the genetic locus required for this activity revealed a putative natural product biosynthetic gene cluster, further defined to a six-gene operon named alb1-alb6. Bioinformatic analysis of the proteins encoded by alb1-6 predicted a hybrid non-ribosomal peptide synthetase-polyketide synthase (NRPS-PKS) assembly line (Alb4/5/6), tailoring enzymes (Alb2/3) and an export/resistance protein (Alb1), and suggested that the machinery assembled althiomycin or a related molecule. Althiomycin is a ribosome-inhibiting antibiotic whose biosynthetic machinery had been elusive for decades. Chromatographic and spectroscopic analyses confirmed that wild type S. marcescens produced althiomycin and that production was eliminated on disruption of the alb gene cluster. Construction of mutants with in-frame deletions of specific alb genes demonstrated that Alb2-Alb5 were essential for althiomycin production, whereas Alb6 was required for maximal production of the antibiotic. A phosphopantetheinyl transferase enzyme required for althiomycin biosynthesis was also identified. Expression of Alb1, a predicted major facilitator superfamily efflux pump, conferred althiomycin resistance on another, sensitive, strain of S. marcescens. This is the first report of althiomycin production outside of the Myxobacteria or Streptomyces and paves the way for future exploitation of the biosynthetic machinery, since S. marcescens represents a convenient and tractable producing organism.

U2 - 10.1371/journal.pone.0044673

DO - 10.1371/journal.pone.0044673

M1 - Article

JO - PLoS ONE

JF - PLoS ONE

IS - 9

VL - 7

SP - e44673

ER -

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