Enzymes in spider venoms show bioeconomic potential

The growing world population is an ever-increasing problem. New, sustainable solutions are urgently being sought to cover the global consumption of foodstuffs. One possible solution is the development of new enzyme technologies. At the Fraunhofer IME in Giessen, the "Animal Venomics" group is focusing on a completely new, untapped source of enzymes: spider venoms.

Spiders have inhabited almost all terrestrial ecosystems for the past 300 million years. With ~ 52,000 documented species, many of which venomous, they are among the most successful venomous animals. Besides spiders, the arachnid clade encompasses scorpions, pseudoscorpions and parasitic taxa such as ticks. Spiders are classified into three suborders: Mesothelae, Mygalomorphae and Araneomorphae. The Mesothelae are the most primitive evolutionary group, comprising only a single family (Liphistiidae), while the Mygalomorphae, including tarantulas, encompass ~ 3,000 species. The Araneomorphae constitute the most extensive suborder, encompassing approximately 94% of extant spider species, and include a considerable diversity, such as the wasp spider (Argiope bruennichi) and the black widow (Latrodectus mactans).

© Tobias Hauke
Image of the yellow sac spider (Cheiracanthium punctorium)

The biochemical diversity of spider venoms

With the exception of the Uloboridae family, all spiders are capable of producing venom in specialized venom glands and inject it into the victim through biting tools. The composition of spider venoms is intricate, comprising up to 3,000 distinct biomolecules, including neurotoxins, antimicrobial peptides and enzymes. These components act both individually and synergistically to produce a powerful effect on the victim. The principal effect of most spider venoms on their victim is to affect the nervous system, resulting in paralysis and, in some cases, death. Neurotoxins disrupt the transmission of stimuli via involved ion channels and receptors in neurons. Furthermore, enzymes can perform a variety of functions, including the dissemination of the toxin throughout the victim's body.

Due to the presence of diverse components, spider venoms are an important reservoir of novel natural substances. It is estimated that over 10 million biomolecules could be extracted from spider venoms, yet less than 3,000 toxins have been described to date. This discrepancy can partly be attributed to the conventional approach, which includes a great deal of effort and has been mainly applied to larger spider species. Modern Venomics, an approach based on 'omics technologies', has overcome this limitation. Omics technologies encompass the analysis of proteins (proteomics), genomes (genomics), metabolites (metabolomics) and transcriptomes (transcriptomics). The integration of transcriptomics and proteomics, underpinned by bioinformatics, facilitates the elucidation of the toxin composition. In comparison with conventional methodologies, this approach necessitates only minute quantities of crude venom or isolated venom glands, thereby rendering the analysis of previously inaccessible venoms feasible.

Enzymes from Spider Venoms: Potential for Industrial Applications

Our working group "Animal Venomics" investigates enzymes present in spider venoms. While there is some scientific evidence for the presence of enzymes in spider venoms, no systematic search has yet been carried out. Utilizing a comprehensive analysis of existing raw data, our research has identified over 140 distinct enzyme families. This finding calls into question previous assumptions regarding the complexity of spider venoms and offers novel perspectives for the potential applications of these enzymes. They are of interest for a variety of industrial applications due to their ability to function under conditions of high chemical variation. This can be attributed to the strong difference between production and storage conditions compared to their active forms. Consequently, these enzymes hold potential for application in diverse fields, including the food industry, cleaning agents, and the textile industry. For instance, the presence of peptidases, amylases and lipases in spider venoms suggests their potential application in cleaning agents, where they could be used to remove stains or break down organic waste. Furthermore, the potential of peroxidases as antimicrobial additives or for the removal of excess dyes in the textile industry is a promising avenue for further research.

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Analysis of spider venoms and heterologous production of toxins for potential applications

Establishment of Enzyme Production Using Omics Technologies

The advent of novel "omics technologies" has facilitated the identification of a plethora of intriguing toxin components, which hold considerable promise for utilization in diverse industrial sectors. However, in order to evaluate this potential, it is necessary to provide these enzymes in sufficient quantities. This necessitates the targeted enzyme production. Our group focuses on the development of a synthesis method for enzymes within bacterial cells. Bacteria are a suitable system due to their easy handling, scalability and the availability of established laboratory protocols. The amino acid sequence of the enzymes can be determined by means of 'omics technologies'. To produce the enzyme, the sequence must be introduced into the bacterial cells. To ensure a handling as safe as possible, the enzymes are inactivated by adding further proteins. Following the successful introduction of the genetic information into the bacterial cells, they are capable of producing the inactive enzyme. Subsequent purification and activation of the inactivated enzyme is achieved by the removal of the additives. Following a further purification step, the active enzyme is obtained and its potential evaluated.

Whilst the research community has hitherto concentrated exclusively on the medical and agricultural applications of spider venom enzymes, this area of research has the potential to lead to new and exciting discoveries. However, given that less than one percent of spider venoms have been the subject of study to date, there are many exciting discoveries to be made in this field. Advancements in 'omics technologies' and heterologous production in bacteria are offering novel perspectives that extend far beyond traditional areas of application.

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In addition to biobanking, our methods include a portfolio of systems biology methods (bottom-up and top-down proteomics, transcriptomics and genomics) and various approaches to heterologous protein expression as well as expertise in the implementation and adaptation of in vitro and in vivo bioassays. Furthermore, we have expertise in protein engineering and the application of various bioinformatic tools for effective bioprospecting from animal toxins.

Workgroup »Animal Venomics«

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