Cryptic Chemical Variation in a Marine Red Alga as Revealed by Nontargeted Metabolomics

• Type of Material: Article
• Authors: Bhuwan Khatri Chhetri, Georgia Institute of Technology; Nazia Mojib, Spelman College; Samuel G Moore, Georgia Institute of Technology; David A Delgadillo, California Institute of Technology; Jessica E Burch, California Institute of Technology; Nolan H Barrett, School of Earth and Atmospheric Sciences; David A Gaul, Georgia Institute of Technology; Lewis Marquez, Emory University; Katy Soapi, University of the South Pacific; Hosea M Nelson, California Institute of Technology; Cassandra Quave, Emory University; Julia Kubanek, Georgia Institute of Technology
• Language: English
• Date: 2023-04-06
• Publisher: AMER CHEMICAL SOC
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Published by American Chemical Society
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1021/acsomega.3c00301
• Title of Journal or Parent Work: ACS OMEGA
• Volume: 8
• Issue: 15
• Start Page: 13899
• End Page: 13910
• Keywords: Physical Sciences; Chemistry, Multidisciplinary; Science & Technology; Chemistry

Abstract

Many marine algae occupy habitats that are dark, deep, or encrusted on other organisms and hence are frequently overlooked by natural product chemists. However, exploration of less-studied organisms can lead to new opportunities for drug discovery. Genetic variation at the individual, species, genus, and population levels as well as environmental influences on gene expression enable expansion of the chemical repertoire associated with a taxonomic group, enabling natural product exploration using innovative analytical methods. A nontargeted LC-MS and 1H NMR spectroscopy-based metabolomic study of 32 collections of representatives of the calcareous red algal genus Peyssonnelia from coral reef habitats in Fiji and the Solomon Islands revealed significant correlations between natural products’ chemistry, phylogeny, and biomedically relevant biological activity. Hierarchical cluster analysis (HCA) of LC-MS data in conjunction with NMR profiling and MS/MS-based molecular networking revealed the presence of at least four distinct algal chemotypes within the genus Peyssonnelia. Two Fijian collections were prioritized for further analysis, leading to the isolation of three novel sulfated triterpene glycosides with a rearranged isomalabaricane carbon skeleton, guided by the metabolomic data. The discovery of peyssobaricanosides A-C (15-17) from two Fijian Peyssonnelia collections, but not from closely related specimens collected in the Solomon Islands that were otherwise chemically and phylogenetically very similar, alludes to population-level variation in secondary metabolite production. Our study reinforces the significance of exploring unusual ecological niches and showcases marine red algae as a chemically rich treasure trove.