Detailed Mechanistic Study of the Non-enzymatic Formation of the Discoipyrrole Family of Natural Products

Dominic A. Colosimo, John B. Macmillan

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Discoipyrroles A-D (DPA-DPD) are recently discovered natural products produced by the marine bacterium Bacillus hunanensis that exhibit anticancer properties in vitro. Initial biosynthetic studies demonstrated that DPA is formed in the liquid fermentation medium of B. hunanensis from three secreted metabolites through an unknown but protein-independent mechanism. The increased identification of natural products that depend on non-enzymatic steps creates a significant need to understand how these different reactions can occur. In this work, we utilized 15N-labeled starting materials and continuous high-sensitivity 1H-15N HMBC NMR spectroscopy to resolve scarce reaction intermediates of the non-enzymatic discoipyrrole reaction as they formed in real time. This information guided supplemental experiments using 13C- and 18O-labeled materials to elucidate the details of DPA's non-enzymatic biosynthesis, which features a highly concerted pyrrole formation and necessary O2-mediated oxidation. We have illustrated a novel way of using isotopically enhanced two-dimensional NMR spectroscopy to interrogate reaction mechanisms as they occur. In addition, these findings add to our growing knowledge of how multicomponent non-enzymatic reactions can occur through inherently reactive bacterial metabolites.

Original languageEnglish (US)
Pages (from-to)2383-2388
Number of pages6
JournalJournal of the American Chemical Society
Volume138
Issue number7
DOIs
StatePublished - Mar 2 2016

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Metabolites
Biological Products
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
Reaction intermediates
Pyrroles
Biosynthesis
Bacilli
Fermentation
Bacillus
Bacteria
Proteins
Oxidation
Liquids
Experiments
discoipyrrole A
In Vitro Techniques
discoipyrrole D

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Detailed Mechanistic Study of the Non-enzymatic Formation of the Discoipyrrole Family of Natural Products. / Colosimo, Dominic A.; Macmillan, John B.

In: Journal of the American Chemical Society, Vol. 138, No. 7, 02.03.2016, p. 2383-2388.

Research output: Contribution to journalArticle

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