LC-MS/MS Strategy Using Substructure Searching for the Annotation of Cyanopeptide Classes: Implications for New Compound Discovery and Environmental Monitoring

June 20, 2026 | Runjie Xia, Lindsey Ahn, Michaela Burkhauser, Ross Youngs, Matthew J. Bertin*

Abstract

Cyanobacterial harmful algal blooms (cyanoHABs) are a major ecological and public health concern, commonly monitored for hepatotoxic microcystins and cylindrospermopsins and neurotoxic anatoxins and saxitoxins. However, the broader suite of bioactive metabolites produced during blooms remains undercharacterized. Here, we interrogated a chromatography fraction library generated from a cyanoHAB in Muskegon, Michigan.

© 2026 The Authors. Published by American Chemical Society

Introduction

Cyanobacterial harmful algal blooms (cyanoHABs) are expanding globally and represent a persistent threat to water quality and human health through the production of toxic secondary metabolites. In most freshwater systems, monitoring and risk management are centered on microcystins, a structurally diverse family of hepatotoxins that is the basis for international guidance values and U.S. drinking-water health advisories. However, the current monitoring approach does not capture the broader metabolite mixtures produced during blooms, which is increasingly being shown in more and more studies.

Cyanobacteria generate extensive suites of “cyanometabolites”, including numerous cyanopeptides assembled by nonribosomal peptide synthetases and other biosynthetic pathways, such as micropeptins/cyanopeptolins, anabaenopeptins, microviridins, microginins, and others in addition to the large class of microcystins. These compounds can exhibit potent bioactivities and may influence ecological interactions, food-web transfer, and human exposure profiles.