Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus

Sheng Huang, Yudong Zhao, Zhiwei Qin, Xiaoling Wang, Mayca Onega, Li Chen, Jing He, Yi Yu (Corresponding Author), Hai Deng (Corresponding Author)

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Holomycin is a dithiolopyrrolone antibiotic natural product produced by Streptomyces clavuligerus, ATCC 27064. This paper reports on the identification of a gene cluster from S. clavuligerus that directs holomycin biosynthesis. Heterologous expression of the cluster in S. albus then induced the production of holomycin. Bioinformatics analysis of the gene cluster revealed that holomycin was assembled by a single multidomain non-ribosomal peptide synthetase (NRPS) consisting of heterocyclization, adenylation, and thiolation domains (Cy-A-T), a free-standing condensation domain, two thioesterases, five tailoring enzymes involved in oxidative reactions and two regulatory and transcriptional genes. Knock out of the gene, HomI, completely abolished the production of holomycin, which is consistent with its role as a key biosynthetic gene and is likely involved in the formation of the disulfide bond generating the final precursor, holothin.
Original languageEnglish
Pages (from-to)811-816
Number of pages6
JournalProcess Biochemistry
Volume46
Issue number3
Early online date8 Dec 2010
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Streptomyces
Multigene Family
Genes
Peptide Synthases
Gene Knockout Techniques
Biosynthesis
Antibiotics
Regulator Genes
Bioinformatics
Computational Biology
Biological Products
Disulfides
Peptides
Condensation
Enzymes
holomycin
Anti-Bacterial Agents

Keywords

  • Dithiolopyrrolone
  • Holomycin
  • NRPS
  • Heterologous expression
  • Biosynthesis

Cite this

Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus. / Huang, Sheng ; Zhao, Yudong ; Qin, Zhiwei; Wang, Xiaoling; Onega, Mayca; Chen, Li ; He, Jing ; Yu, Yi (Corresponding Author); Deng, Hai (Corresponding Author).

In: Process Biochemistry, Vol. 46, No. 3, 03.2011, p. 811-816.

Research output: Contribution to journalArticle

Huang, Sheng ; Zhao, Yudong ; Qin, Zhiwei ; Wang, Xiaoling ; Onega, Mayca ; Chen, Li ; He, Jing ; Yu, Yi ; Deng, Hai. / Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus. In: Process Biochemistry. 2011 ; Vol. 46, No. 3. pp. 811-816.
@article{976d542233f944c8918ab3762606387c,
title = "Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus",
abstract = "Holomycin is a dithiolopyrrolone antibiotic natural product produced by Streptomyces clavuligerus, ATCC 27064. This paper reports on the identification of a gene cluster from S. clavuligerus that directs holomycin biosynthesis. Heterologous expression of the cluster in S. albus then induced the production of holomycin. Bioinformatics analysis of the gene cluster revealed that holomycin was assembled by a single multidomain non-ribosomal peptide synthetase (NRPS) consisting of heterocyclization, adenylation, and thiolation domains (Cy-A-T), a free-standing condensation domain, two thioesterases, five tailoring enzymes involved in oxidative reactions and two regulatory and transcriptional genes. Knock out of the gene, HomI, completely abolished the production of holomycin, which is consistent with its role as a key biosynthetic gene and is likely involved in the formation of the disulfide bond generating the final precursor, holothin.",
keywords = "Dithiolopyrrolone, Holomycin, NRPS, Heterologous expression, Biosynthesis",
author = "Sheng Huang and Yudong Zhao and Zhiwei Qin and Xiaoling Wang and Mayca Onega and Li Chen and Jing He and Yi Yu and Hai Deng",
note = "Acknowledgements YY thanks Professor Meifeng Tao for providing the strain Streptomyces clavuligerus, ATCC 27064. YY was supported by the Fundamental Research Funds for the Central Universities, China (Grant No. 52204-09064) and the “Dawn” Program of Wuhan Science and Technology Bureau for Young Scholars, China (Grant No. 4006-106016). HD thanks the School of Natural and Computing Sciences, University of Aberdeen for a Ph.D. studentship (XLW) and Drs A. Raab and Rainer Ebel for High resolution LC–MS analysis.",
year = "2011",
month = "3",
doi = "10.1016/j.procbio.2010.11.024",
language = "English",
volume = "46",
pages = "811--816",
journal = "Process Biochemistry",
issn = "1359-5113",
publisher = "Elsevier BV",
number = "3",

}

TY - JOUR

T1 - Identification and heterologous expression of the biosynthetic gene cluster for holomycin produced by Streptomyces clavuligerus

AU - Huang, Sheng

AU - Zhao, Yudong

AU - Qin, Zhiwei

AU - Wang, Xiaoling

AU - Onega, Mayca

AU - Chen, Li

AU - He, Jing

AU - Yu, Yi

AU - Deng, Hai

N1 - Acknowledgements YY thanks Professor Meifeng Tao for providing the strain Streptomyces clavuligerus, ATCC 27064. YY was supported by the Fundamental Research Funds for the Central Universities, China (Grant No. 52204-09064) and the “Dawn” Program of Wuhan Science and Technology Bureau for Young Scholars, China (Grant No. 4006-106016). HD thanks the School of Natural and Computing Sciences, University of Aberdeen for a Ph.D. studentship (XLW) and Drs A. Raab and Rainer Ebel for High resolution LC–MS analysis.

PY - 2011/3

Y1 - 2011/3

N2 - Holomycin is a dithiolopyrrolone antibiotic natural product produced by Streptomyces clavuligerus, ATCC 27064. This paper reports on the identification of a gene cluster from S. clavuligerus that directs holomycin biosynthesis. Heterologous expression of the cluster in S. albus then induced the production of holomycin. Bioinformatics analysis of the gene cluster revealed that holomycin was assembled by a single multidomain non-ribosomal peptide synthetase (NRPS) consisting of heterocyclization, adenylation, and thiolation domains (Cy-A-T), a free-standing condensation domain, two thioesterases, five tailoring enzymes involved in oxidative reactions and two regulatory and transcriptional genes. Knock out of the gene, HomI, completely abolished the production of holomycin, which is consistent with its role as a key biosynthetic gene and is likely involved in the formation of the disulfide bond generating the final precursor, holothin.

AB - Holomycin is a dithiolopyrrolone antibiotic natural product produced by Streptomyces clavuligerus, ATCC 27064. This paper reports on the identification of a gene cluster from S. clavuligerus that directs holomycin biosynthesis. Heterologous expression of the cluster in S. albus then induced the production of holomycin. Bioinformatics analysis of the gene cluster revealed that holomycin was assembled by a single multidomain non-ribosomal peptide synthetase (NRPS) consisting of heterocyclization, adenylation, and thiolation domains (Cy-A-T), a free-standing condensation domain, two thioesterases, five tailoring enzymes involved in oxidative reactions and two regulatory and transcriptional genes. Knock out of the gene, HomI, completely abolished the production of holomycin, which is consistent with its role as a key biosynthetic gene and is likely involved in the formation of the disulfide bond generating the final precursor, holothin.

KW - Dithiolopyrrolone

KW - Holomycin

KW - NRPS

KW - Heterologous expression

KW - Biosynthesis

U2 - 10.1016/j.procbio.2010.11.024

DO - 10.1016/j.procbio.2010.11.024

M3 - Article

VL - 46

SP - 811

EP - 816

JO - Process Biochemistry

JF - Process Biochemistry

SN - 1359-5113

IS - 3

ER -