Spider: digestive enzymes and venom may have the same origin – 10/31/2023 – Science

The genus spiders Uloborus they lost their poison a few million years ago. However, they have such powerful digestive juice that, when they regurgitate it to begin digesting immobilized prey, they protect their own legs. Without this care, they could be left without their front paws during the meal.

In a study published in the journal Scientific Reports, researchers from the Butantan Institute and the Federal University of Uberlândia (UFU) found proteins in this digestive juice that are also present in the venom of other spiders — these are still venomous.

The result suggests that both digestive and venom enzymes may have a common evolutionary origin.

“As other families of spiders that also release this liquid onto their prey are venomous, venom was attributed with the ability to break down molecules into smaller fractions to facilitate digestion. However, this family [Uloboridae] lost the glands that produce poison a long time ago. It is clear, therefore, that this external digestion is an exclusive function of the enzymes in this digestive liquid”, says Rodrigo Valladão, first author of the article and doctoral candidate at the Biochemistry Laboratory of the Butantan Institute.

The study is part of the project “Enzymology and molecular physiology in Arachnida”, supported by Fapesp and coordinated by Adriana Rios Lopes at Butantan.

“These spiders wrap their prey in meters of web and then regurgitate digestive fluid over them, which degrades both the web and insects and other animals, sometimes larger than the spider itself. The prey’s tissues become liquid and easier to digest. digest”, explains Lopes, who supervises Valladão’s doctorate.

The study is the first characterization ever made of the molecules involved in the digestive process and the contents of the midgut (where the juice is formed) of a non-venomous spider.

The content of the digestive juice of Uloborus includes enzymes such as hydrolases, catalysts that use water to break chemical bonds. Among the hydrolases, peptidases, which break down peptides, were detected; carbohydrases, responsible for breaking down carbohydrates (sugars), and lipases, which break down fats (lipids).

In addition, 50 proteins have been characterized as enzymes, structural proteins or toxins, many present in both venomous and non-poisonous species. One of them, sphingomyelinase D, for example, had until then only been found in poisons.

Anticoagulant potential

In another study by the Butantan group, published in the same journal, six molecules were identified with the potential to inhibit the activity of serine peptidases, important enzymes in several human physiological processes. One of the molecules is from a new structural class of inhibitors.

The discovery paves the way, for example, for the search for anticoagulant agents that can be used in pharmaceuticals and cosmetics.

The discovered inhibitors are part of the giant spider’s digestive fluid (Nephilingis cruentata), a species that is harmless to humans, but that injects poison into insects and also expels liquid that digests the prey outside the body.

In 2016, the group had shown that it was the juice regurgitated by giant spiders that carried out this digestion. Until then, it was thought that it was mainly the poison that performed this function (read more here).

“This molecule is not familiar with other classic serine peptidase inhibitors described in the literature, presenting a new structural pattern. Therefore, it has the potential to perform functions in a different way from those already known by the pharmaceutical industry. The next steps of the research will be produce the inhibitor using recombinant DNA technologies and explore possible applications, such as the effects on blood clotting”, says Oscar Bento da Silva Neto, first author of the study, which began during his undergraduate studies with the support of a scholarship from Fapesp. Currently, Silva Neto is pursuing a doctorate at the Biochemistry Laboratory of the Butantan Institute under the guidance of Lopes.

Analysis of the amino acid sequences of this inhibitor indicates that the new molecules may be present in the digestive systems of other spiders. Its function would be to inactivate trypsin —a serine peptidase— contained in prey, which could harm spiders when ingested.

“There are several processes in human physiology that depend on specific enzymes, such as serine peptidases, involved in coagulation. New anticoagulants have long been sought, important for surgeries, for example. As this is a new family of inhibitors, it has pharmacological potential” , highlights Lopes.

Another potential application, says the researcher, would be in medicines or cosmetics for skin diseases, such as allergies and atopic dermatitis, which are increasingly common and do not have many therapeutic options. New studies, however, need to be carried out to verify the real potential of the new molecules.

The article “Digestive Enzymes and Sphingomyelinase D in Spiders Without Venom (Uloboridae)” [Uloboridae])” can be accessed here.

The publication “Spiders’ Digestive System as a Source of Trypsin Inhibitors: Functional Activity of a Member of Atracotoxin Structural Family” is available here.