ArticleNature communications2022
Bifurcation drives the evolution of assembly-line biosynthesis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Mapping the nonribosomal specificity code through promiscuity-guided A-domain engineering.Chemical science · 2026Article
- Paenidepsins are a Family of Lipopeptides fromJournal of natural products · 2026Article
- The undiscovered natural product potential of Actinomycetes.The Journal of antibiotics · 2026Article
- Non-ribosomal peptide cyclase-directed chemoenzymatic synthesis of lariat lipopeptides.Nature chemistry · 2026Article
- Thiotemplated Polyketide Chain Fusion and Reductive Cyclization Build the Reactive Butenolide Core of Malleicyprol.Angewandte Chemie (International ed. in English) · 2025Article
- Mixing and Matching of Hybrid Megasynthases is a Hub for the Evolution of Metabolic Diversity in Cyanobacteria.Angewandte Chemie (International ed. in English) · 2025Article
- Synthetic Biology in Natural Product Biosynthesis.Chemical reviews · 2025Review
- Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution.mSystems · 2025Review
- Pangenome mining of the Streptomyces genus redefines species' biosynthetic potential.Genome biology · 2025Article
- Macrocyclizing-thioesterases in bacterial non-ribosomal peptide biosynthesis.Journal of natural medicines · 2025Review
- Natural diversifying evolution of nonribosomal peptide synthetases in a defensive symbiont reveals nonmodular functional constraints.PNAS nexus · 2024Article
- Chemoenzymatic tandem cyclization for the facile synthesis of bicyclic peptides.Communications chemistry · 2024Article
- Metagenomic domain substitution for the high-throughput modification of nonribosomal peptides.Nature chemical biology · 2024Article
- Phylogenetic reconciliation: making the most of genomes to understand microbial ecology and evolution.The ISME journal · 2024Review
- Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization.Beilstein journal of organic chemistry · 2024Review
- Total substitution and partial modification of the set of non-ribosomal peptide synthetases clusters lead to pyoverdine diversity in theFrontiers in microbiology · 2024Article
- Biocatalytic cyclization of small macrolactams by a penicillin-binding protein-type thioesterase.Nature chemical biology · 2024Article
- Nonribosomal Peptide Synthesis Definitely Working Out of the Rules.Microorganisms · 2022Review
- Complex peptide natural products: Biosynthetic principles, challenges and opportunities for pathway engineering.Synthetic and systems biotechnology · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.