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Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster

Author

Listed:
  • Yunzi Luo

    (University of Illinois at Urbana-Champaign)

  • Hua Huang

    (University of Illinois at Urbana-Champaign)

  • Jing Liang

    (University of Illinois at Urbana-Champaign)

  • Meng Wang

    (University of Illinois at Urbana-Champaign)

  • Lu Lu

    (University of Illinois at Urbana-Champaign)

  • Zengyi Shao

    (University of Illinois at Urbana-Champaign)

  • Ryan E. Cobb

    (University of Illinois at Urbana-Champaign
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

  • Huimin Zhao

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    Institute for Genomic Biology, University of Illinois at Urbana-Champaign)

Abstract

Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of these PTMs have not been characterized. Here we apply a plug-and-play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from Streptomyces griseus and discover three new PTMs. This gene cluster is highly conserved in phylogenetically diverse bacterial strains and contains an unusual hybrid polyketide synthase-nonribosomal peptide synthetase, which resembles iterative polyketide synthases known in fungi. To further characterize this gene cluster, we use the same synthetic biology approach to create a series of gene deletion constructs and elucidate the biosynthetic steps for the formation of the polycyclic system. The strategy we employ bypasses the traditional laborious processes to elicit gene cluster expression and should be generally applicable to many other silent or cryptic gene clusters for discovery and characterization of new natural products.

Suggested Citation

  • Yunzi Luo & Hua Huang & Jing Liang & Meng Wang & Lu Lu & Zengyi Shao & Ryan E. Cobb & Huimin Zhao, 2013. "Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster," Nature Communications, Nature, vol. 4(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3894
    DOI: 10.1038/ncomms3894
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    Cited by:

    1. Leixia Chu & Xiaoxia Luo & Taoting Zhu & Yingying Cao & Lili Zhang & Zixin Deng & Jiangtao Gao, 2022. "Harnessing phosphonate antibiotics argolaphos biosynthesis enables a synthetic biology-based green synthesis of glyphosate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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