title: Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species.
abstract: Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. Here we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains, including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated the identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. These efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches.
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Katherine R
authors: KR
authors: Duncan
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Max
authors: M
authors: Crüsemann
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Anna
authors: A
authors: Lechner
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Anindita
authors: A
authors: Sarkar
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Jie
authors: J
authors: Li
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
authors: Nadine
authors: N
authors: Ziemert
authors: Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
authors: Mingxun
authors: M
authors: Wang
authors: Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
authors: Nuno
authors: N
authors: Bandeira
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, Departments of Pharmacology, Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: bsmoore@ucsd.edu.
authors: Bradley S
authors: BS
authors: Moore
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, Departments of Pharmacology, Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: pdorrestein@ucsd.edu.
authors: Pieter C
authors: PC
authors: Dorrestein
authors: Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: pjensen@ucsd.edu.
authors: Paul R
authors: PR
authors: Jensen
mesh_terms: D002851:Chromatography, High Pressure Liquid; D047630:Depsipeptides / Q000096:biosynthesis; D016680:Genome, Bacterial; D023281:Genomics; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D055442:Metabolome; D008848:Micromonosporaceae / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D047630:Depsipeptides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase