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A

bout 100 different microalgae species produce marine

toxins, which are a food safety concern because they

produce acute intoxications which are sometimes lethal.

There are about 1,000 different marine structures, potentially

many more, and their presence in certain species of fish, bivalves

and seafood causes several thousand intoxications every year.

Climate change is expanding the range of these toxins, as we have

recently discovered for tetrodotoxin and ciguatoxins, and some of

them, which are considered tropical, now have a constant

presence in southern European coasts.

In the past years, we have dedicated an important effort to

developing fast

in vitro

methods to detect and quantify these

toxins because their high toxicity requires a constant monitoring

of their presence by the authorities and producers. Our approach

has always been the same: once we identify the receptor target

to the toxin group, we use this receptor as

a binder to an

in vitro

assay.

We have developed methods for all the

toxin groups, represented by their

reference compounds saxitoxin, okadaic

acid, ciguatoxin, palytoxin, spirolide,

yessotoxin, pectenotoxin and brevetoxin.

We did not develop methods for domoic

acid, as the analysis is fairly simple, or for

azaspiracid, since the mechanism of

action of this group is as yet unknown.

For each of the groups the technologies used ranged from

biosensors, such as the resonant mirror or the surface plasmon

resonance, to polarisation fluorescence or radioactivity.

The main advantage of using receptors instead of antibodies is

that receptors are able to detect any compound with the same

mechanism of action, without the limitation of cross-reactivity

typical of antibodies. Therefore, we have focused on development

based on the binding to sodium-potassium ATPase (palytoxins,

ovatoxins, ostreocins), phosphodiesterase 4 (yessotoxins), sodium

channels (saxitoxin, gonyautoxins, ciguatoxin, brevetoxin,

gambierona), actin (pectenotoxin), nicotinic receptors (spirolides

and cyclic imines), and phosphatase 2A (okadaic acid and

dinophysis toxins).

Given the fact that once the target is identified it is possible to

study how it is modulated, a natural evolution to our work was to

identify the potential therapeutic consequences of this

modulation. The results were quite surprising as marine toxins

are incredible molecules, both in terms of their structures and

their effects. Our work has been the consequence of a fruitful

The research of Dr Luis M Botana’s group has centred on marine toxins for the

past 25 years, and has also explored the potential of these molecules as drug

leads for therapeutic applications

Marine toxins, new drugs

122

I S S U E S E V E N

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L

www.horizon2020projects.com

P R O F I L E

B I O T E C H N O L O G Y F O R H E A L T H

Dr Luis M Botana

Fig. 1 Structure of palytoxin (up), the largest non-polymeric compound in

Nature and as toxic as botulinum toxin; yessotoxin (down), a marine

compound with many potential therapeutic uses; and the research group

Fig. 2 Microalgae

Gambierdiscus,

producer of ciguatoxins, a tropical

toxin now present in southern Europe and active on sodium channels