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; Hai Deng

doi:10.1016/j.procbio.2010.11.024

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^* (Corresponding Author), Yi Yu^* (Corresponding Author), Hai Deng^* (Corresponding Author)

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

27 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 language	English
Pages (from-to)	811-816
Number of pages	6
Journal	Process Biochemistry
Volume	46
Issue number	3
Early online date	8 Dec 2010
DOIs	https://doi.org/10.1016/j.procbio.2010.11.024
Publication status	Published - Mar 2011

Bibliographical 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.

Keywords

Dithiolopyrrolone
Holomycin
NRPS
Heterologous expression
Biosynthesis

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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.",

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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.

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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.

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KW - Heterologous expression

KW - Biosynthesis

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DO - 10.1016/j.procbio.2010.11.024

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SN - 1359-5113

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JO - Process Biochemistry

JF - Process Biochemistry

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

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