CyanoMetDB, a comprehensive public database of secondary metabolites from cyanobacteria

Martin R Jones,Ernani Pinto,Mariana A Torres,Fabiane Dörr,Hanna Mazur-Marzec,Karolina Szubert,Luciana Tartaglione,Carmela Dell'Aversano,Christopher O Miles,Daniel G Beach,Pearse Mccarron,Kaarina Sivonen,David P Fewer,Jouni Jokela,Elisabeth M.-L Janssen

doi:10.1016/j.watres.2021.117017

Abstract

Harmful cyanobacterial blooms, which frequently contain toxic secondary metabolites, are reported in aquatic environments around the world. More than two thousand cyanobacterial secondary metabolites have been reported from diverse sources over the past fifty years. A comprehensive, publically-accessible database detailing these secondary metabolites would facilitate research into their occurrence, functions and toxicological risks. To address this need we created CyanoMetDB, a highly curated, flat-file, openly-accessible database of cyanobacterial secondary metabolites collated from 850 peer-reviewed articles published between 1967 and 2020. CyanoMetDB contains 2010 cyanobacterial metabolites and 99 structurally related compounds. This has nearly doubled the number of entries with complete literature metadata and structural composition information compared to previously available open access databases. The dataset includes microcytsins, cyanopeptolins, other depsipeptides, anabaenopeptins, microginins, aeruginosins, cyclamides, cryptophycins, saxitoxins, spumigins, microviridins, and anatoxins among other metabolite classes. A comprehensive database dedicated to cyanobacterial secondary metabolites facilitates: (1) the detection and dereplication of known cyanobacterial toxins and secondary metabolites; (2) the identification of novel natural products from cyanobacteria; (3) research on biosynthesis of cyanobacterial secondary metabolites, including substructure searches; and (4) the investigation of their abundance, persistence, and toxicity in natural environments.

Highlights

Around the globe, cyanobacteria inhabit fresh waters including drinking water reservoirs, brackish waters, and marine environments where they can proliferate to form harmful blooms
CyanoMetDB is a flat-file database comprising the following core fields: compound identifier, compound name, compound class, molecular formula, molecular weight, monoisotopic mass, primary reference that elucidated the structure, detailed structural information as a simplified molecular input line entry system (SMILES codes) and other structural codes that serve as chemical identifiers for each compound (InChl, InChlKey, IUPAC names), whether an NMR platform was used for structure elucidation, and information about the sample used to elucidate the structure of the compound, see Table 2.8 Entries in the database correspond to compounds reported as cyanobacterial metabolites
The rapid increase during the 1990s was, in part, likely associated with the discovery that microcystins pose significant hepatotoxic risks to humans, which in turn lead to MC-LR being included in the World Health Organization’s water quality guidelines, prompting significant research on cyanobacteria

Summary

Introduction

Cyanobacteria inhabit fresh waters including drinking water reservoirs, brackish waters, and marine environments where they can proliferate to form harmful blooms. During these events, cyanobacteria can produce high concentrations of a diverse mixture of rather unique secondary metabolites. Research into analytical and toxicological methods relies on a comprehensive understanding of the structural information of cyanobacterial metabolites. While information from commercial databases of secondary metabolites are only accessible to paying customers (e.g., Antibase, MarinLit, The Dictionary of Natural Products), several open-access databases exist but are often limited regarding the number cyanobacterial metabolites or parameters listed (e.g., ALGALTOX List, NORINE database, Handbook of Marine Natural Products).. The “Cyanomet mass” list by LeManach et al (2019) contains 852 entries, of which 35 belong to the class of microcystins and nearly 500 compounds are listed with complete molecular formulae and literature reference but no further structural information is given. The Natural Product Atlas (2019) contains a similar number of entries for cyanobacterial metabolites, including microcystins, and provides structural codes (e.g., SMILES code) and the stereochemistry is known for 768 entries

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