Nerpa: A Tool for Discovering Biosynthetic Gene Clusters of Bacterial Nonribosomal Peptides

Metabolites

卷:11

Anton Korobeynikov¹  Azat M. Tagirdzhanov¹  Olga Kunyavskaya¹  Alexey Gurevich¹  Andrés Mauricio Caraballo-Rodríguez²  Louis-Félix Nothias²  Pieter C. Dorrestein²  Hosein Mohimani³ 

[1] Center for Algorithmic Biotechnology, Saint Petersburg State University, Saint Petersburg 199004, Russia;

[2] Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA;

[3] Computational Biology Department, School of Computer Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA;

关键词: natural products;    nonribosomal peptides;    genome mining;    biosynthetic gene clusters;    bioinformatics;    mass spectrometry;   

DOI  :  10.3390/metabo11100693

来源: DOAJ

【 摘 要 】

Microbial natural products are a major source of bioactive compounds for drug discovery. Among these molecules, nonribosomal peptides (NRPs) represent a diverse class of natural products that include antibiotics, immunosuppressants, and anticancer agents. Recent breakthroughs in natural product discovery have revealed the chemical structure of several thousand NRPs. However, biosynthetic gene clusters (BGCs) encoding them are known only for a few hundred compounds. Here, we developed Nerpa, a computational method for the high-throughput discovery of novel BGCs responsible for producing known NRPs. After searching 13,399 representative bacterial genomes from the RefSeq repository against 8368 known NRPs, Nerpa linked 117 BGCs to their products. We further experimentally validated the predicted BGC of ngercheumicin from Photobacterium galatheae via mass spectrometry. Nerpa supports searching new genomes against thousands of known NRP structures, and novel molecular structures against tens of thousands of bacterial genomes. The availability of these tools can enhance our understanding of NRP synthesis and the function of their biosynthetic enzymes.

【 授权许可】

Unknown