TY - JOUR

T1 - A Maldiisotopic Approach to Discover Natural Products

T2 - Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium Moorea producens

AU - Kinnel, Robin B.

AU - Esquenazi, Eduardo

AU - Leao, Tiago

AU - Moss, Nathan

AU - Mevers, Emily

AU - Pereira, Alban R.

AU - Monroe, Emily A.

AU - Korobeynikov, Anton

AU - Murray, Thomas F.

AU - Sherman, David

AU - Gerwick, Lena

AU - Dorrestein, Pieter C.

AU - Gerwick, William H.

PY - 2017/5/26

Y1 - 2017/5/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85019766761&partnerID=8YFLogxK

U2 - 10.1021/acs.jnatprod.7b00019

DO - 10.1021/acs.jnatprod.7b00019

M3 - Article

C2 - 28448144

AN - SCOPUS:85019766761

VL - 80

SP - 1514

EP - 1521

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 5

ER -