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

The Journal of Antibioticsvolume 71pages495505 (2018) | Download Citation

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.

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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.

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Author notes

  1. Bee Gek Ng and Jae Woo Han contributed equally to this work

Affiliations

  1. Department of Biotechnology, Korea University Graduate School, Seoul, Korea

    • Bee Gek Ng
    •  & Beom Seok Kim
  2. Korea Research Institute of Chemical Technology, Center for Eco-Friendly New Materials, Daejeon, Seoul, Korea

    • Jae Woo Han
    •  & Gyung Ja Choi
  3. Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea

    • Dong Wan Lee
    •  & Beom Seok Kim

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The authors declare that they have no conflict of interest.

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Correspondence to Beom Seok Kim.

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DOI

https://doi.org/10.1038/s41429-017-0023-x