Bifurcation drives the evolution of assembly-line biosynthesis

  • 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.
Metadaten
Author:Thomas J. BoothORCiD, Kenan A. J. BozhüyükORCiDGND, Jonathon D. ListonORCiD, Sibyl F. D. BateyORCiD, Ernest LaceyORCiD, Barrie WilkinsonORCiDGND
URN:urn:nbn:de:hebis:30:3-632642
DOI:https://doi.org/10.1038/s41467-022-30950-z
ISSN:2041-1723
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Date of Publication (online):2022/06/17
Date of first Publication:2022/06/17
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/02/20
Tag:Bacterial genes; Biosynthesis; Evolutionary genetics
Volume:13
Issue:art. 3498
Article Number:3498
Page Number:12
First Page:1
Last Page:12
Note:
Data availability
Data supporting the findings of this work are available within the paper and its Supplementary Information file, or in publicly available databases. The DNA sequence data for the genome assembly and biosynthetic gene clusters (BGCs) generated in this study have been deposited in GenBank. The genome sequence of Streptomyces sp. MST-110588 has been deposited under the accession code GenBank: CP074380. The desotamide BGCs have been deposited under the accession codes as follows: Streptomyces sp. MST-70754, GenBank: MZ093610; Streptomyces sp. MST-71321, GenBank: MZ093611; Streptomyces sp. MST-71458, GenBank: MZ093612; Streptomyces sp. MST-94754, GenBank: MZ093613; and Streptomyces sp. MST-127221, GenBank: MZ093614. The crystal structure coordinates of the docking domain protein PaxC_NDD–PaxB_CDD were retrieved from the RSCB Protein Data Bank file PDB-ID: 6TRP_1 [https://doi.org/10.2210/pdb6trp/pdb. Biochemical data for analysis of adenylation-domain substrate specificity are available as a Source Data file. A reporting summary for this Article is available as a Supplementary Information file. Source data are provided with this paper.
Note:
This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) via Strategic Program Project BBS/E/J/000PR9790 to the John Innes Centre, and by Norwich Research Park Doctoral Training Program Studentship BB/J014524/1 to T.J.B.) and BB/M011216/1 (to J.D.L.). We also acknowledge the support of the Cooperative Research Centres Projects Scheme (CRCPFIVE000119) (to E.L.).
HeBIS-PPN:50718176X
Institutes:Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International

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