Abstract Title

The neurotoxin 2,4-diaminobutanoic acid (2,4-DAB): genomic insights into how and why it is biosynthesised in some cyanobacteria

Start Date

24-5-2022 5:45 PM

End Date

24-5-2022 7:00 PM

Abstract

Cyanobacteria are an ancient clade of photosynthetic prokaryotes, whose worldwide occurrence presents health hazards to humans and animals due to the production of a range of toxins (cyanotoxins). These include the non-encoded diaminoacid neurotoxin 2,4-diaminobutanoic acid (2,4-diaminobutyric acid; 2,4-DAB), which can be lethal to aquatic biota and mammals. Knowledge of the biosynthetic pathway(s) to this cyanotoxin, and its role(s) in cyanobacteria, is lacking. Here, we use bioinformatics analyses to investigate hypotheses concerning neurotoxin biosynthesis in 130 cyanobacterial genomes. The presence of enzymes potentially involved in toxin production was assessed via profile hidden Markov models, sequence alignment, substrate specificity/active site identification and gene tree reconstruction. The co-localisation of these enzymes within specialised metabolite clusters known to be involved in toxin production was also considered. We show that, in cyanobacteria, the biosynthesis of 2,4-DAB appears to be either restricted to some species, or there may be multiple and additional routes, and roles, for its biosynthesis. For species where this neurotoxin can be biosynthesised enzymatically, an association with siderophore and polyamine production appears to be present in some species. We extend our comparative genomics analyses to some other toxins.

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May 24th, 5:45 PM May 24th, 7:00 PM

The neurotoxin 2,4-diaminobutanoic acid (2,4-DAB): genomic insights into how and why it is biosynthesised in some cyanobacteria

Cyanobacteria are an ancient clade of photosynthetic prokaryotes, whose worldwide occurrence presents health hazards to humans and animals due to the production of a range of toxins (cyanotoxins). These include the non-encoded diaminoacid neurotoxin 2,4-diaminobutanoic acid (2,4-diaminobutyric acid; 2,4-DAB), which can be lethal to aquatic biota and mammals. Knowledge of the biosynthetic pathway(s) to this cyanotoxin, and its role(s) in cyanobacteria, is lacking. Here, we use bioinformatics analyses to investigate hypotheses concerning neurotoxin biosynthesis in 130 cyanobacterial genomes. The presence of enzymes potentially involved in toxin production was assessed via profile hidden Markov models, sequence alignment, substrate specificity/active site identification and gene tree reconstruction. The co-localisation of these enzymes within specialised metabolite clusters known to be involved in toxin production was also considered. We show that, in cyanobacteria, the biosynthesis of 2,4-DAB appears to be either restricted to some species, or there may be multiple and additional routes, and roles, for its biosynthesis. For species where this neurotoxin can be biosynthesised enzymatically, an association with siderophore and polyamine production appears to be present in some species. We extend our comparative genomics analyses to some other toxins.