Natural Product Domain Seeker

np2_intro_2021

NaPDoS2 Features

  • NaPDoS2, the second-generation Natural Product Domain Seeker, rapidly detects and classifies ketosynthase (KS) and condensation (C) domains from genomic, metagenomic, or PCR amplicon sequence data.
  • Biosynthetic potential is assessed using short KS and C domain sequence tags, enabling rapid analysis of large datasets without the need for complete, fully assembled biosynthetic gene clusters (BGCs).
  • A phylogeny-based classification scheme is used to make broader predictions about the polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes in which these domains are found, including specific product classification assignments.
  • NaPDoS2 provides major speed and accuracy improvements compared to legacy NaPDoS (version 1), along with greatly expanded taxonomic and functional diversity in KS classification categories (Klau et al. 2022).
Please check out our quick start page for instructions on how to run analyses and interpret results. More details and a complete tutorial are provided in our full documentation file (right-click link to download).

If you find NaPDoS useful for your work, please cite:

Klau LJ, Podell S, Creamer KE, Demko AM, Singh HW, Allen EE, Moore BS, Ziemert N, Letzel AC, Jensen PR. (2022) The Natural Product Domain Seeker version 2 (NaPDoS2) webtool relates ketosynthase phylogeny to biosynthetic function. Journal of Biological Chemistry. https://doi.org/10.1016/j.jbc.2022.102480.


What Are Natural Products?

Natural products are specialized organic compounds produced by living organisms. They are generally not considered essential for normal growth or reproduction but instead have ecological functions related to communication, defense, competition, and reproduction among others. Natural products are an important source of medicines including antibiotics and anticancer agents (Li and Vederas 2009) and were traditionally discovered using bioassays to guide their isolation. Ready access to DNA sequence data, coupled with a better understanding of the genetic basis of natural product biosynthesis, has created opportunities to develop sequence-based approaches to natural product discovery (Zerikly et al. 2009; Blin et al. 2021).

Polyketide Synthases and Nonribosomal Peptide Synthetases

PKS and NRPS BGCs account for many of the most important natural products discovered to date (Fischbach and Walsh 2006). The enzymes encoded by these BGCs assemble polyketides and nonribosomal peptides from simple carboxylic acid and amino acid building blocks, respectively. KS and C domains play critical roles in the assembly process by covalently joining extender units in polyketide biosynthesis and catalyzing peptide bond formation in non-ribosomal peptide biosynthesis. Importantly, KS and C domain phylogenies have proven highly informative of PKS and NRPS organization and function (Rausch et al. 2007; Jenke-Kodama and Dittmann 2009; Jenke-Kodama et al. 2005; Metsa-Ketela et al. 2002). These phylogeny based predictions form the basis of the NaPDoS2 classification scheme (Ziemert et al. 2012; Klau et al. 2022).

Additional references