The Natural Product Domain Seeker version 2 (NaPDoS2) webtool relates ketosynthase phylogeny to biosynthetic function.

Content Provider	Europe PMC
Author	Klau, Leesa J. Podell, Sheila Creamer, Kaitlin E. Demko, Alyssa M. Singh, Hans W. Allen, Eric E. Moore, Bradley S. Ziemert, Nadine Letzel, Anne Catrin Jensen, Paul R.
Copyright Year	2022
Abstract	The Natural Product Domain Seeker (NaPDoS) webtool detects and classifies ketosynthase (KS) and condensation domains from genomic, metagenomic, and amplicon sequence data. Unlike other tools, a phylogeny-based classification scheme is used to make broader predictions about the polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) genes in which these domains are found. NaPDoS is particularly useful for the analysis of incomplete biosynthetic genes or gene clusters, as are often observed in poorly assembled genomes and metagenomes, or when loci are not clustered, as in eukaryotic genomes. To help support the growing interest in sequence-based analyses of natural product biosynthetic diversity, here we introduce version 2 of the webtool, NaPDoS2, available at http://napdos.ucsd.edu/napdos2. This update includes the addition of 1417 KS sequences, representing a major expansion of the taxonomic and functional diversity represented in the webtool database. The phylogeny-based KS classification scheme now recognizes 41 class and subclass assignments, including new type II PKS subclasses. Workflow modifications accelerate run times, allowing larger datasets to be analyzed. In addition, default parameters were established using statistical validation tests to maximize KS detection and classification accuracy while minimizing false positives. We further demonstrate the applications of NaPDoS2 to assess PKS biosynthetic potential using genomic, metagenomic, and PCR amplicon datasets. These examples illustrate how NaPDoS2 can be used to predict biosynthetic potential and detect genes involved in the biosynthesis of specific structure classes or new biosynthetic mechanisms.
ISSN	00219258
Volume Number	298
PubMed Central reference number	PMC9582728
Issue Number	10
PubMed reference number	36108739
Journal	The Journal of Biological Chemistry [J. Biol. Chem]
e-ISSN	1083351X
DOI	10.1016/j.jbc.2022.102480
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2022-09-12
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2022 The Authors
Subject Keyword	ACP, acyl carrier protein BGC, biosynthetic gene cluster C, condensation ECH, enoyl-CoA hydratase ER, enoyl reductase FAS, fatty acid synthase HR, highly reducing KS, ketosynthase NaPDoS, Natural Product Domain Seeker NRPS, nonribosomal peptide synthetase NR, nonreducing PKS, polyketide synthase PUFA, polyunsaturated fatty acid PTM, polycyclic tetramate macrolactam trans-AT, trans-acyl transferase
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry