15N Stable Isotope Labeling and Comparative Metabolomics Facilitates Genome Mining in Cultured Cyanobacteria

ACS Chemical Biology
2020.0

Abstract

As genome mining becomes a more widely used approach to identify bacterial natural products, the challenge of matching biosynthetic gene clusters to their cognate secondary metabolites has become more apparent. Bioinformatic platforms such as AntiSMASH have made great progress in predicting chemical structures from genetic information, however the predicted structures are often incomplete. This complicates identifying the predicted compounds by mass spectrometry. Secondary metabolites produced by cyanobacteria represent a unique opportunity for bridging this gap. Cultured cyanobacteria incorporate inorganic nitrogen provided in chemically defined media into all nitrogen-containing secondary metabolites. Thus, stable isotope labeling with (15)N labeled nitrate and subsequent comparative metabolomics can be used to match biosynthetic gene clusters to their cognate compounds in cell extracts. Analysis of the sequenced genome of Nostoc sp. UIC 10630 identified six biosynthetic gene clusters predicted to encode the production of a secondary metabolite with at least one nitrogen atom. Comparative metabolomic analysis of the (15)N labeled and unlabeled cell extracts revealed four nitrogen containing compounds that contained the same number of nitrogen atoms as were predicted in the biosynthetic gene clusters. Two of the four compounds were new secondary metabolites, and their structures were elucidated by NMR, HRESIMS, and MS/MS.

Knowledge Graph

Similar Paper

<sup>15</sup>N Stable Isotope Labeling and Comparative Metabolomics Facilitates Genome Mining in Cultured Cyanobacteria
ACS Chemical Biology 2020.0
Discovery of Cyanobacterial Natural Products Containing Fatty Acid Residues**
Angewandte Chemie International Edition 2021.0
Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria
Journal of Natural Products 2015.0
Combining Mass Spectrometric Metabolic Profiling with Genomic Analysis: A Powerful Approach for Discovering Natural Products from Cyanobacteria
Journal of Natural Products 2015.0
An isotopic labeling approach linking natural products with biosynthetic gene clusters
Nature Chemical Biology 2022.0
Expanding the Described Metabolome of the Marine Cyanobacterium Moorea producens JHB through Orthogonal Natural Products Workflows
PLOS ONE 2015.0
A Maldiisotopic Approach to Discover Natural Products: Cryptomaldamide, a Hybrid Tripeptide from the Marine Cyanobacterium <i>Moorea producens</i>
Journal of Natural Products 2017.0
Analysis of the cyanobacterial amino acid metabolism with a precise genome-scale metabolic reconstruction of Anabaena sp. UTEX 2576
Biochemical Engineering Journal 2021.0
Unlocking the Spatial Control of Secondary Metabolism Uncovers Hidden Natural Product Diversity in <i>Nostoc punctiforme</i>
ACS Chemical Biology 2019.0
New Antibacterial Metabolites from the Cyanobacterium <i>Nostoc </i><i>c</i><i>ommune </i>(EAWAG 122b)
Journal of Natural Products 2000.0