ArticlePloS one2013
Classification of the adenylation and acyl-transferase activity of NRPS and PKS systems using ensembles of substrate specific hidden Markov models.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 92 citations in OpenAlex.
- Dissection and Engineering of Modular Polyketide Synthase Extender Unit Specificity Motifs.Chembiochem : a European journal of chemical biology · 2026Article
- PARAS: High-Accuracy Machine Learning of Substrate Specificities in Nonribosomal Peptide Synthetases.JACS Au · 2026Article
- Feature sequence-based genome mining uncovers the hidden diversity of bacterial siderophore pathways.eLife · 2024Article
- Genome Mining for Diazo-Synthesis-Related Genes inBiomolecules · 2024Article
- Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases.Marine drugs · 2024Review
- Structural, biochemical and bioinformatic analyses of nonribosomal peptide synthetase adenylation domains.Natural product reports · 2024Review
- Non-ribosomal peptide synthetase (NRPS)-encoding products and their biosynthetic logics in Fusarium.Microbial cell factories · 2024Review
- Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond.Beilstein journal of organic chemistry · 2024Article
- Knowledge-guided data mining on the standardized architecture of NRPS: Subtypes, novel motifs, and sequence entanglements.PLoS computational biology · 2023Article
- Unique Initiation and Termination Mechanisms Involved in the Biosynthesis of a Hybrid Polyketide-Nonribosomal Peptide Lyngbyapeptin B Produced by the Marine CyanobacteriumACS chemical biology · 2023Article
- Bioinformatic Analysis Reveals both Oversampled and Underexplored Biosynthetic Diversity in Nonribosomal Peptides.ACS chemical biology · 2023Article
- Endofungal bacteria boost anthelminthic host protection with the biosurfactant symbiosin.Chemical science · 2022Article
- Evolutionary Genome Mining for the Discovery and Engineering of Natural Product Biosynthesis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Genetic Relationships in the Toxin-Producing Fungal Endophyte,Journal of fungi (Basel, Switzerland) · 2021Article
- Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase.Nature communications · 2021Article
- Diversity of Polyketide Synthases and Nonribosomal Peptide Synthetases Revealed Through Metagenomic Analysis of a Deep Oligotrophic Cave.Microbial ecology · 2021Article
- SeMPI 2.0-A Web Server for PKS and NRPS Predictions Combined with Metabolite Screening in Natural Product Databases.Metabolites · 2020Article
- The Genome of the Plant-Associated Lactic Acid Bacterium Lactococcus lactis KF147 Harbors a Hybrid NRPS-PKS System Conserved in Strains of the Dental Cariogenic Streptococcus mutans.Current microbiology · 2020Article
- Advances in linking polyketides and non-ribosomal peptides to their biosynthetic gene clusters in Fusarium.Current genetics · 2019Review
- Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code.ACS chemical biology · 2019Article
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Authors and funding
4 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
There is a growing interest in the Non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) of microbes, fungi and plants because they can produce bioactive peptides such as antibiotics. The ability to identify the substrate specificity of the enzyme's adenylation (A) and acyl-transferase (AT) domains is essential to rationally deduce or engineer new products. We here report on a Hidden Markov Model (HMM)-based ensemble method to predict the substrate specificity at high quality. We collected a new reference set of experimentally validated sequences. An initial classification based on alignment and Neighbor Joining was performed in line with most of the previously published prediction methods. We then created and tested single substrate specific HMMs and found that their use improved the correct identification significantly for A as well as for AT domains. A major advantage of the use of HMMs is that it abolishes the dependency on multiple sequence alignment and residue selection that is hampering the alignment-based clustering methods. Using our models we obtained a high prediction quality for the substrate specificity of the A domains similar to two recently published tools that make use of HMMs or Support Vector Machines (NRPSsp and NRPS predictor2, respectively). Moreover, replacement of the single substrate specific HMMs by ensembles of models caused a clear increase in prediction quality. We argue that the superiority of the ensemble over the single model is caused by the way substrate specificity evolves for the studied systems. It is likely that this also holds true for other protein domains. The ensemble predictor has been implemented in a simple web-based tool that is available at http://www.cmbi.ru.nl/NRPS-PKS-substrate-predictor/.
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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.