DOI

Peptidic natural products (PNPs) include many antibiotics and other bioactive compounds. While the recent launch of the Global Natural Products Social (GNPS) molecular networking infrastructure is transforming PNP discovery into a high-throughput technology, PNP identification algorithms are needed to realize the potential of the GNPS project. GNPS relies on the assump- tion that each connected component of a molecular network (representing related metabolites) illuminates the ‘dark matter of metabolomics’ as long as it contains a known metabolite present in a database. We reveal a surprising diversity of PNPs produced by related bacteria and show that, contrary to the ‘comparative metabolomics’ assumption, two related bacteria are unlikely to produce identical PNPs (even though they are likely to produce similar PNPs). Since this observation undermines the utility of GNPS, we developed a PNP identification tool, VarQuest, that illuminates the connected components in a molecular network even if they do not contain known PNPs and only contain their variants. VarQuest reveals an order of magnitude more PNP variants than all previous PNP discovery efforts and demonstrates that GNPS already contains spectra from 41% of the currently known PNP families. The enormous diversity of PNPs suggests that biosynthetic gene clusters in various microorgan- isms constantly evolve to generate a unique spectrum of PNP variants that differ from PNPs in other species.
Язык оригиналаанглийский
Страницы (с-по)319-327
Число страниц9
ЖурналNature Microbiology
Том3
Номер выпуска3
DOI
СостояниеОпубликовано - 1 мар 2018

    Предметные области Scopus

  • Прикладная микробиология и биотехника
  • Микробиология (медицинская)
  • Генетика
  • Клеточная биология
  • Микробиология
  • Иммунология

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