Timo Niedermeyer | From well-known to unknown cyanotoxins

Timo Niedermeyer - Martin-Luther-University Halle-Wittenberg, Germany
Homepage: ag-bioarznei.pharmazie.uni-ha...
Twitter: / niedermeyer_lab
From well-known to unknown cyanotoxins: Microcystins as leads for drug substances and the identification of the novel cyanotoxin Aetokthonotoxin
Cyanobacteria are famous for the production of toxins such as microcystins, anatoxins, or cylindrospermopsins. However, “toxin” is just a synonym for “compound with impressing biological activity”. None of the drug substances on the market today is free of toxicity if misused. Thus, also cyanobacterial “toxins” can serve as lead compounds for drug development. Microcystins, potent inhibitors of protein phosphatases, are known as toxins causing severe liver damage. Due to their pronounced cytotoxicity, they could potentially be used as anti-cancer drugs. In the first part of the talk, I will present our work in this field. Using precursor-directed biosynthesis, we have developed easy-to-derivatize microcystins that can e.g. be used as biochemical probes or be coupled to monoclonal antibodies as payloads in antibody-drug conjugates (ADCs) for targeted cancer therapy. Vacuolar Myelinopathy (VM) is a fatal neurological disease that has been observed in water birds, raptors, and other animals throughout the south-eastern US since 1994. It is spreading and has already affected thousands of animals, including the iconic bald eagle. Previous studies could link the disease to the occurrence of Aetokthonos hydrillicola, a novel cyanobacterial genus that grows epiphytically on water plants such as Hydrilla verticillata. Despite years of work, the putative cyanobacterial toxin remained elusive. In the second part of the talk, I will present the isolation and identification of a novel penta-brominated bisindole alkaloid, Aetokthonotoxin (AETX), that we showed to be the cyanotoxin causing VM.
Paper:
AETX project
doi.org/10.1126/science.aax9050
doi.org/10.1002/chem.202101848
Microcystin project
doi.org/10.1371/journal.pone....
doi.org/10.1021/acs.jnatprod....
This talk is part of the CyanoWorld online seminar series, hosted by Nicolas Schmelling and Ilka Axmann, and was held on Zoom on June 10th, 2021.
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11:00 the eleventh min.