ArticlePLoS computational biology2014
A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed.
- Temporal dynamics of gut biosynthetic gene clusters link persistent colonization and engraftment in fecal microbiota transplantation.Gut microbes · 2026Article
- Drift, selection and recombination bias drive the evolution of a non-ribosomal peptide.Nature ecology & evolution · 2026Article
- Inter-species horizontal transfer of biosynthetic gene clusters: an evolutionary driver for chemical diversity in bacterial communities.Essays in biochemistry · 2026Review
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- Evolutionary diversification of polyketide synthase (PKS) enzymes in Monascus purpureus strains for exploitation as a molecular factory.Archives of microbiology · 2026Article
- Genome Mining-Guided Discovery of the Glycosylated Griseorhodin Congener Ruskamycin.Journal of natural products · 2026Article
- BisCEET: A Visual Browser for Biosynthetic Gene Clusters Aiding in the Identification of Natural Product Variants and Distinct Tailoring Enzymes.Journal of natural products · 2026Article
- The Incredible Potential of Cave Actinobacteria in Finding New Antimicrobials and Bioactive Compounds.Chemistry & biodiversity · 2026Review
- Mapping the nonribosomal specificity code through promiscuity-guided A-domain engineering.Chemical science · 2026Article
- Article
- Biocontrol Efficacy and Genomic Basis of Endophytic Bacteria AgainstLife (Basel, Switzerland) · 2026Article
- Skeletal editing via multi-step engineering of a modular polyketide synthase.Nature communications · 2026Article
- Marine Bacteria as a Source of Antibiotics AgainstMarine drugs · 2026Review
- Eco-evolutionary dynamics sustain a potent yet rare antibiotic gene cluster in Streptomyces.The ISME journal · 2026Article
- Chromosome-level genome assembly ofHorticulture research · 2026Article
- Molecular biology and integrated strategies for activating cryptic biosynthetic gene clusters toward next-generation antibiotic discovery.Frontiers in bioinformatics · 2026Review
- Benchmarking methods for measuring biosynthetic gene cluster similarity and determination of gene cluster families.Bioinformatics (Oxford, England) · 2025Article
- Evolutionary Tree in Chemical Space of Natural Products.bioRxiv : the preprint server for biology · 2025Article
- Gene conversion-associated successive engineering of modular polyketide synthases.Communications chemistry · 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
64 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
Abstract
Bacterial secondary metabolites are widely used as antibiotics, anticancer drugs, insecticides and food additives. Attempts to engineer their biosynthetic gene clusters (BGCs) to produce unnatural metabolites with improved properties are often frustrated by the unpredictability and complexity of the enzymes that synthesize these molecules, suggesting that genetic changes within BGCs are limited by specific constraints. Here, by performing a systematic computational analysis of BGC evolution, we derive evidence for three findings that shed light on the ways in which, despite these constraints, nature successfully invents new molecules: 1) BGCs for complex molecules often evolve through the successive merger of smaller sub-clusters, which function as independent evolutionary entities. 2) An important subset of polyketide synthases and nonribosomal peptide synthetases evolve by concerted evolution, which generates sets of sequence-homogenized domains that may hold promise for engineering efforts since they exhibit a high degree of functional interoperability, 3) Individual BGC families evolve in distinct ways, suggesting that design strategies should take into account family-specific functional constraints. These findings suggest novel strategies for using synthetic biology to rationally engineer biosynthetic pathways.
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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.