The Metabolome of a Cyanobacterial Bloom Visualized by MS/MS-Based Molecular Networking Reveals New Neurotoxic Smenamide Analogs (C, D, and E).

Christopher W Via,Samuel Costa,Matthew J Bertin,Peter D R Moeller,William H Gerwick,Paul V Zimba,Evgenia Glukhov

doi:10.3389/fchem.2018.00316

Abstract

Members of the cyanobacterial genus Trichodesmium are well known for their substantial impact on nitrogen influx in ocean ecosystems and the enormous surface blooms they form in tropical and subtropical locations. However, the secondary metabolite composition of these complex environmental bloom events is not well known, nor the possibility of the production of potent toxins that have been observed in other bloom-forming marine and freshwater cyanobacteria species. In the present work, we aimed to characterize the metabolome of a Trichodesmium bloom utilizing MS/MS-based molecular networking. Furthermore, we integrated cytotoxicity assays in order to identify and ultimately isolate potential cyanotoxins from the bloom. These efforts led to the isolation and identification of several members of the smenamide family, including three new smenamide analogs (1–3) as well as the previously reported smenothiazole A-hybrid polyketide-peptide compounds. Two of these new smenamides possessed cytotoxicity to neuro-2A cells (1 and 3) and their presence elicits further questions as to their potential ecological roles. HPLC profiling and molecular networking of chromatography fractions from the bloom revealed an elaborate secondary metabolome, generating hypotheses with respect to the environmental role of these metabolites and the consistency of this chemical composition across genera, space and time.

Highlights

IntroductionBlooms of toxin-producing cyanobacteria (harmful algal blooms, HABs) continue to be a threat to water resources in the U.S and across the globe (Carmichael and Boyer, 2016)
Blooms of toxin-producing cyanobacteria continue to be a threat to water resources in the U.S and across the globe (Carmichael and Boyer, 2016)
Members of the bloom-forming genus Trichodesmium are an understudied group of marine cyanobacteria with respect to toxin production and environmental impact

Summary

Introduction

Blooms of toxin-producing cyanobacteria (harmful algal blooms, HABs) continue to be a threat to water resources in the U.S and across the globe (Carmichael and Boyer, 2016) Research surrounding these bloom events with respect to cyanobacteria has generally focused on freshwater planktonic species and a suite of well-characterized toxins, including the anatoxins, saxitoxins and microcystins (Bláha et al, 2009). The lipoamides, credneramides A and B were isolated and characterized from a field-collected benthic cyanobacterium identified as a new species of Trichodesmium (Malloy et al, 2012) These metabolites inhibited spontaneous calcium oscillations in murine cerebrocortical neurons (Malloy et al, 2012). Several known cyanotoxins, such as anatoxin, saxitoxin, microcystins and aplysiatoxins have been reported from Trichodesmium blooms collected from distinct geographic areas (Ramos et al, 2005; Detoni et al, 2016; Shunmugam et al, 2017)

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