ArticleProceedings of the National Academy of Sciences of the United States of America2021
GRINS: Genetic elements that recode assembly-line polyketide synthases and accelerate their diversification.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 23 citations in OpenAlex.
- Evolutionary strategies of late-stage diversification in bacterial biosynthetic gene clusters.Essays in biochemistry · 2026Review
- 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
- Context matters: assessing the impacts of genomic background and ecology on microbial biosynthetic gene cluster evolution.mSystems · 2025Review
- zol and fai: large-scale targeted detection and evolutionary investigation of gene clusters.Nucleic acids research · 2025Article
- Conjugation Mediates Large-Scale Chromosomal Transfer in Streptomyces Driving Diversification of Antibiotic Biosynthetic Gene Clusters.Molecular biology and evolution · 2024Article
- Structure and Mechanisms of Assembly-Line Polyketide Synthases.Annual review of biochemistry · 2024Review
- Module-Based Polyketide Synthase Engineering forACS synthetic biology · 2023Review
- Effects of Epigenetic Modification and High Hydrostatic Pressure on Polyketide Synthase Genes and Secondary Metabolites ofMarine drugs · 2023Article
- Genomic mining and diversity of assembly line polyketide synthases.Open biology · 2023Article
- Deep self-supervised learning for biosynthetic gene cluster detection and product classification.PLoS computational biology · 2023Article
- Enzymology of assembly line synthesis by modular polyketide synthases.Nature chemical biology · 2023Review
- Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition.Nature communications · 2023Article
- Selection for constrained peptides that bind to a single target protein.Nature communications · 2021Article
- QnAs with Chaitan Khosla.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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4 authors at 1 institution in 1 country.
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Abstract
Assembly-line polyketide synthases (PKSs) are large and complex enzymatic machineries with a multimodular architecture, typically encoded in bacterial genomes by biosynthetic gene clusters. Their modularity has led to an astounding diversity of biosynthesized molecules, many with medical relevance. Thus, understanding the mechanisms that drive PKS evolution is fundamental for both functional prediction of natural PKSs as well as for the engineering of novel PKSs. Here, we describe a repetitive genetic element in assembly-line PKS genes which appears to play a role in accelerating the diversification of closely related biosynthetic clusters. We named this element GRINS: genetic repeats of intense nucleotide skews. GRINS appear to recode PKS protein regions with a biased nucleotide composition and to promote gene conversion. GRINS are present in a large number of assembly-line PKS gene clusters and are particularly widespread in the actinobacterial genus
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