A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens

Robin B. Kinnel, Eduardo Esquenazi, Tiago Leao, Nathan Moss, Emily Mevers, Alban R. Pereira, Emily A. Monroe, Anton Korobeynikov, Thomas F. Murray, David Sherman, Lena Gerwick, Pieter C. Dorrestein, William H. Gerwick

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Genome sequencing of microorganisms has revealed a greatly increased capacity for natural products biosynthesis than was previously recognized from compound isolation efforts alone. Hence, new methods are needed for the discovery and description of this hidden secondary metabolite potential. Here we show that provision of heavy nitrogen 15N-nitrate to marine cyanobacterial cultures followed by single-filament MALDI analysis over a period of days was highly effective in identifying a new natural product with an exceptionally high nitrogen content. The compound, named cryptomaldamide, was subsequently isolated using MS to guide the purification process, and its structure determined by 2D NMR and other spectroscopic and chromatographic methods. Bioinformatic analysis of the draft genome sequence identified a 28.7 kB gene cluster that putatively encodes for cryptomaldamide biosynthesis. Notably, an amidinotransferase is proposed to initiate the biosynthetic process by transferring an amidino group from arginine to serine to produce the first residue to be incorporated by the hybrid NRPS-PKS pathway. The maldiisotopic approach presented here is thus demonstrated to provide an orthogonal method by which to discover novel chemical diversity from Nature.

Original languageEnglish (US)
Pages (from-to)1514-1521
Number of pages8
JournalJournal of Natural Products
Volume80
Issue number5
DOIs
StatePublished - May 26 2017

Fingerprint

Cyanobacteria
Biological Products
Genes
Biosynthesis
Amidinotransferases
Nitrogen
Genome
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Bioinformatics
Multigene Family
Metabolites
Computational Biology
Microorganisms
Nitrates
Serine
Purification
Arginine
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

A Maldiisotopic Approach to Discover Natural Products : Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens. / Kinnel, Robin B.; Esquenazi, Eduardo; Leao, Tiago; Moss, Nathan; Mevers, Emily; Pereira, Alban R.; Monroe, Emily A.; Korobeynikov, Anton; Murray, Thomas F.; Sherman, David; Gerwick, Lena; Dorrestein, Pieter C.; Gerwick, William H.

In: Journal of Natural Products, Vol. 80, No. 5, 26.05.2017, p. 1514-1521.

Research output: Contribution to journalArticle

Kinnel, RB, Esquenazi, E, Leao, T, Moss, N, Mevers, E, Pereira, AR, Monroe, EA, Korobeynikov, A, Murray, TF, Sherman, D, Gerwick, L, Dorrestein, PC & Gerwick, WH 2017, 'A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens', Journal of Natural Products, vol. 80, no. 5, pp. 1514-1521. https://doi.org/10.1021/acs.jnatprod.7b00019
Kinnel, Robin B. ; Esquenazi, Eduardo ; Leao, Tiago ; Moss, Nathan ; Mevers, Emily ; Pereira, Alban R. ; Monroe, Emily A. ; Korobeynikov, Anton ; Murray, Thomas F. ; Sherman, David ; Gerwick, Lena ; Dorrestein, Pieter C. ; Gerwick, William H. / A Maldiisotopic Approach to Discover Natural Products : Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens. In: Journal of Natural Products. 2017 ; Vol. 80, No. 5. pp. 1514-1521.
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