The chejuenolide biosynthetic gene cluster harboring an iterative trans-AT PKS system in Hahella chejuensis strain MB-1084

Bee Gek Ng; Jae Woo Han; Dong Wan Lee; Gyung Ja Choi; Beom Seok Kim

doi:10.1038/s41429-017-0023-x

The chejuenolide biosynthetic gene cluster harboring an iterative trans-AT PKS system in Hahella chejuensis strain MB-1084

Bee Gek Ng, Jae Woo Han, Dong Wan Lee, Gyung Ja Choi, Beom Seok Kim

Department of Biosystems and Biotechnology

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

5 Citations (Scopus)

Abstract

Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog. Based on the results, we found that the che PKSs have non-canonical features such as trans-AT system and insufficient number of KS domains (five KS domains) for chejuenolide production (requires eight rounds of Claisen condensation reaction). Heterologous expression of the che PKSs in the E. coli BAP1 strain provides strong evidence of the iterative characteristic of the modular PKSs. Additionally, the phylogenetic relatedness of the KS domains of che PKSs and other trans-AT PKSs was analyzed to propose a possible pathway for chejuenolide biosynthesis.

Original language	English
Pages (from-to)	495-505
Number of pages	11
Journal	Journal of Antibiotics
Volume	71
Issue number	5
DOIs	https://doi.org/10.1038/s41429-017-0023-x
Publication status	Published - 2018 May 1

Bibliographical note

Funding Information:
This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel Jorn from Department of Biology, ETH Zurich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101

Funding Information:
Acknowledgements This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel Jörn from Department of Biology, ETH Zürich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101.

Publisher Copyright:
© 2018 The Author(s) [YEAR], under exclusive licence to the Japan Antibiotics Research Association.

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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title = "The chejuenolide biosynthetic gene cluster harboring an iterative trans-AT PKS system in Hahella chejuensis strain MB-1084",

abstract = "Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog. Based on the results, we found that the che PKSs have non-canonical features such as trans-AT system and insufficient number of KS domains (five KS domains) for chejuenolide production (requires eight rounds of Claisen condensation reaction). Heterologous expression of the che PKSs in the E. coli BAP1 strain provides strong evidence of the iterative characteristic of the modular PKSs. Additionally, the phylogenetic relatedness of the KS domains of che PKSs and other trans-AT PKSs was analyzed to propose a possible pathway for chejuenolide biosynthesis.",

author = "Ng, {Bee Gek} and Han, {Jae Woo} and Lee, {Dong Wan} and Choi, {Gyung Ja} and Kim, {Beom Seok}",

note = "Funding Information: This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel Jorn from Department of Biology, ETH Zurich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101 Funding Information: Acknowledgements This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel J{\"o}rn from Department of Biology, ETH Z{\"u}rich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101. Publisher Copyright: {\textcopyright} 2018 The Author(s) [YEAR], under exclusive licence to the Japan Antibiotics Research Association.",

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AU - Han, Jae Woo

AU - Lee, Dong Wan

AU - Choi, Gyung Ja

AU - Kim, Beom Seok

N1 - Funding Information: This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel Jorn from Department of Biology, ETH Zurich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101 Funding Information: Acknowledgements This work was supported by a Grant of Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2017R1D1A1B03027996). We sincerely thank Professor Piel Jörn from Department of Biology, ETH Zürich for the advice on phylogenetic analysis, Professor Blaine Pfeifer from Department of Chemical and Biological Engineering, State University of New York for providing the E. coli BAP1 strain and Professor Kim Kun Soo from Department of Life Sciences, Sogang University for providing plasmid pKNG101. Publisher Copyright: © 2018 The Author(s) [YEAR], under exclusive licence to the Japan Antibiotics Research Association.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog. Based on the results, we found that the che PKSs have non-canonical features such as trans-AT system and insufficient number of KS domains (five KS domains) for chejuenolide production (requires eight rounds of Claisen condensation reaction). Heterologous expression of the che PKSs in the E. coli BAP1 strain provides strong evidence of the iterative characteristic of the modular PKSs. Additionally, the phylogenetic relatedness of the KS domains of che PKSs and other trans-AT PKSs was analyzed to propose a possible pathway for chejuenolide biosynthesis.

AB - Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog. Based on the results, we found that the che PKSs have non-canonical features such as trans-AT system and insufficient number of KS domains (five KS domains) for chejuenolide production (requires eight rounds of Claisen condensation reaction). Heterologous expression of the che PKSs in the E. coli BAP1 strain provides strong evidence of the iterative characteristic of the modular PKSs. Additionally, the phylogenetic relatedness of the KS domains of che PKSs and other trans-AT PKSs was analyzed to propose a possible pathway for chejuenolide biosynthesis.

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The chejuenolide biosynthetic gene cluster harboring an iterative trans-AT PKS system in Hahella chejuensis strain MB-1084

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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