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Bifurcation drives the evolution of assembly-line biosynthesis

Author

Listed:
  • Thomas J. Booth

    (John Innes Centre
    University of Western Australia)

  • Kenan A. J. Bozhüyük

    (John Innes Centre
    Goethe University Frankfurt
    Max-Planck-Institute for Terrestrial Microbiology, Department of Natural Products in Organismic Interactions)

  • Jonathon D. Liston

    (John Innes Centre)

  • Sibyl F. D. Batey

    (John Innes Centre)

  • Ernest Lacey

    (Microbial Screening Technologies)

  • Barrie Wilkinson

    (John Innes Centre)

Abstract

Reprogramming biosynthetic assembly-lines is a topic of intense interest. This is unsurprising as the scaffolds of most antibiotics in current clinical use are produced by such pathways. The modular nature of assembly-lines provides a direct relationship between the sequence of enzymatic domains and the chemical structure of the product, but rational reprogramming efforts have been met with limited success. To gain greater insight into the design process, we wanted to examine how Nature creates assembly-lines and searched for biosynthetic pathways that might represent evolutionary transitions. By examining the biosynthesis of the anti-tubercular wollamides, we uncover how whole gene duplication and neofunctionalization can result in pathway bifurcation. We show that, in the case of the wollamide biosynthesis, neofunctionalization is initiated by intragenomic recombination. This pathway bifurcation leads to redundancy, providing the genetic robustness required to enable large structural changes during the evolution of antibiotic structures. Should the new product be non-functional, gene loss can restore the original genotype. However, if the new product confers an advantage, depreciation and eventual loss of the original gene creates a new linear pathway. This provides the blind watchmaker equivalent to the design, build, test cycle of synthetic biology.

Suggested Citation

  • Thomas J. Booth & Kenan A. J. Bozhüyük & Jonathon D. Liston & Sibyl F. D. Batey & Ernest Lacey & Barrie Wilkinson, 2022. "Bifurcation drives the evolution of assembly-line biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30950-z
    DOI: 10.1038/s41467-022-30950-z
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    References listed on IDEAS

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