ArticleProceedings of the National Academy of Sciences of the United States of America2015
Evolution of chemical diversity by coordinated gene swaps in type II polyketide gene clusters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- The evolutionary processes of bacterial aromatic polyketide ketosynthases.Genome biology · 2026Article
- Charting the Biosynthetic Landscape of Hybrid Polyketide-Nonribosomal Peptide-Specialized Lipids.JACS Au · 2026Article
- Integrated Metabolomic and Genomic Insights into Amino Acid Incorporation Within the Hybrid Polyketide-Alkaloid Antibiotic TLN-05220.ACS chemical biology · 2026Article
- Integrated metabolomic and genomic insights into amino acid incorporation within the hybrid polyketide-alkaloid antibiotic TLN-05220.bioRxiv : the preprint server for biology · 2025Article
- A Phosphopantetheinyl Transferase fromACS omega · 2025Article
- Development of a versatile chassis for the efficient production of diverse type II polyketides.Nature communications · 2025Article
- MultiT2: A Tool Connecting the Multimodal Data for Bacterial Aromatic Polyketide Natural Products.ACS omega · 2025Article
- Strategic Acyl Carrier Protein Engineering Enables Functional Type II Polyketide Synthase Reconstitution In Vitro.ACS chemical biology · 2025Article
- An unusual aromatase/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- An updated catalogue of diverse type II polyketide synthase biosynthetic gene clusters captured from large-scale nucleotide databases.Microbial genomics · 2023Article
- Big data mining, rational modification, and ancestral sequence reconstruction inferred multiple xylose isomerases for biorefinery.Science advances · 2023Article
- Mechanism-based cross-linking probes capture the Escherichia coli ketosynthase FabB in conformationally distinct catalytic states.Acta crystallographica. Section D, Structural biology · 2022Article
- Strategies to access biosynthetic novelty in bacterial genomes for drug discovery.Nature reviews. Drug discovery · 2022Review
- Enzymology of standalone elongating ketosynthases.Chemical science · 2022Review
- Engineered Chimeras Unveil Swappable Modular Features of Fatty Acid and Polyketide Synthase Acyl Carrier Proteins.Biochemistry · 2022Article
- Heterologous Expression, Purification, and Characterization of Type II Polyketide Synthase Acyl Carrier Proteins.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Thioesterase-mediated side chain transesterification generates potent Gq signaling inhibitor FR900359.Nature communications · 2021Article
- Oak-Associated Negativicute Equipped with Ancestral Aromatic Polyketide Synthase Produces Antimycobacterial Dendrubins.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Activity Mapping the Acyl Carrier Protein: Elongating Ketosynthase Interaction in Fatty Acid Biosynthesis.Biochemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Natural product biosynthetic pathways generate molecules of enormous structural complexity and exquisitely tuned biological activities. Studies of natural products have led to the discovery of many pharmaceutical agents, particularly antibiotics. Attempts to harness the catalytic prowess of biosynthetic enzyme systems, for both compound discovery and engineering, have been limited by a poor understanding of the evolution of the underlying gene clusters. We developed an approach to study the evolution of biosynthetic genes on a cluster-wide scale, integrating pairwise gene coevolution information with large-scale phylogenetic analysis. We used this method to infer the evolution of type II polyketide gene clusters, tracing the path of evolution from the single ancestor to those gene clusters surviving today. We identified 10 key gene types in these clusters, most of which were swapped in from existing cellular processes and subsequently specialized. The ancestral type II polyketide gene cluster likely comprised a core set of five genes, a roster that expanded and contracted throughout evolution. A key C24 ancestor diversified into major classes of longer and shorter chain length systems, from which a C20 ancestor gave rise to the majority of characterized type II polyketide antibiotics. Our findings reveal that (i) type II polyketide structure is predictable from its gene roster, (ii) only certain gene combinations are compatible, and (iii) gene swaps were likely a key to evolution of chemical diversity. The lessons learned about how natural selection drives polyketide chemical innovation can be applied to the rational design and guided discovery of chemicals with desired structures and properties.
Indexed as
Identifiers
What OpenQuestion holds
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.