Blog on the SBS seminar from Prof Marcel Jaspars written by Jessie Jungels, student from the “Meet the scientists” course
In a world of growing antibiotic resistance and newly emerging diseases (not to mention, Covid-19), drug discovery and development have become more important than ever. Even though nature is one of the best sources for pharmaceutical products, finding new drugs can prove to be difficult. So why not have a look at more unusual places – such as the most extreme environments on earth?
This is what Professor Marcel Jaspars, an organic chemist at the University of Aberdeen, discussed in a recent SBS seminar. For the last 15 years, he and his colleagues have been working on bacteria, fungi and marine invertebrates living in extreme environmental conditions. By combining approaches from biology and chemistry, they identified a whole range of previously undiscovered chemical compounds with potential use as pharmaceuticals.
The reason why microorganisms are such a good source for finding new drugs is because they can directly produce them. Bacteria and other microbes take up substances from their immediate environment and transform them into specialised metabolites. This process of biosynthesis can be very efficient, with some bacterial species having up to 10% of their genome dedicated to metabolite production (Udwary et al., 2007).
In one of their favourite study areas in the Atacama desert, Chile, Marcel and his team collected soil Lentzea bacteria and found that the variety of novel compounds produced by these bacteria was enormous (Rateb et al., 2018). The Atacama desert has in fact been described as one of the driest places in the world, with some locations not ever having recorded a single raindrop. “Going to an extreme environment gives you really amazing chemical diversity”, Marcel said during the seminar. Similarly interesting results were obtained at a study site in Ghana, where Streptomyces bacteria yielded a large amount of new chemicals, including Legonaridin (Rateb et al., 2015).
But what exactly makes extreme environments so attractive for searching for new pharmaceuticals? The answer is that the surviving organisms in such places evolved very special strategies. These can involve the ability to settle in the area at all, but also the competition with other survivors for the already sparse amount of available food. Hence, microbes that live in harsh environments – also known as extremophiles – are thought to produce compounds that are completely new, as a response to their extreme living conditions (Wilson and Brimble, 2008).
One example is the tennis ball ascidian (Synoicum pulmonaria), which inhabits the waters near the coasts in northern Norway. Whilst living in arctic conditions, this invertebrate has been found to produce novel compounds with antibacterial and antifungal properties (Tadesse et al., 2008). Two of these chemicals, with the not so catchy names of Synoxazolidinone A and C, are now undergoing further clinical trials.
Furthermore, organisms dwelling in the deeper ocean layers, such as the pressure-tolerant bacteria Dermacoccus abyssi, are also potential producers of pharmaceutical compounds. Dermacoccus live in the depths of the Mariana trench in the South Pacific, and were found to synthesise a newly identified family of compounds called Dermacozines (Abdel-Mageed et al., 2010). These chemicals appeared to show activity against the trypanosome parasite that causes sleeping sickness in humans.
There are quite a few compounds from extremely arid, cold or deep-sea environments that have good potential for drug development. Several products from extremophiles are already used in biotechnological applications (Giordano, 2020), and the testing of compounds with possible pharmaceutical properties is still on-going.
One would think that this high potential for novelty would give the green light for producing lots of new drugs. However, finding actual compounds that are suitable for further clinical testing isn’t always so easy. Often, the desired biological activity isn’t important enough, or other products of different origin already exist that are simply more effective. Thus, it can sometimes take a long time to find something to work with.
Nevertheless, there have been several success stories from organisms found in extreme environments and we’ll stay tuned for future discoveries!
References
Abdel-Mageed, W.M., Milne, B.F., Wagner, M., Schumacher, M., Sandor, P., Pathom-aree, W., Goodfellow, M., Bull, A.T., Horikoshi, K., Ebel, R., Diederich, M., Fiedler, H.-P., Jaspars, M., 2010. Dermacozines, a new phenazine family from deep-sea dermacocci isolated from a Mariana Trench sediment. Org. Biomol. Chem. 8, 2352–2362. https://doi.org/10.1039/C001445A
Giordano, D., 2020. Bioactive Molecules from Extreme Environments. Mar. Drugs 18, 640. https://doi.org/10.3390/md18120640
Rateb, M.E., Ebel, R., Jaspars, M., 2018. Natural product diversity of actinobacteria in the Atacama Desert. Antonie Van Leeuwenhoek 111, 1467–1477. https://doi.org/10.1007/s10482-018-1030-z
Rateb, M.E., Zhai, Y., Ehrner, E., Rath, C.M., Wang, X., Tabudravu, J., Ebel, R., Bibb, M., Kyeremeh, K., Dorrestein, P.C., Hong, K., Jaspars, M., Deng, H., 2015. Legonaridin, a new member of linaridin RiPP from a Ghanaian Streptomyces isolate. Org. Biomol. Chem. 13, 9585–9592. https://doi.org/10.1039/C5OB01269D
Tadesse, M., Gulliksen, B., Strøm, M.B., Styrvold, O.B., Haug, T., 2008. Screening for antibacterial and antifungal activities in marine benthic invertebrates from northern Norway. J. Invertebr. Pathol. 99, 286–293. https://doi.org/10.1016/j.jip.2008.06.009
Udwary, D.W., Zeigler, L., Asolkar, R.N., Singan, V., Lapidus, A., Fenical, W., Jensen, P.R., Moore, B.S., 2007. Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc. Natl. Acad. Sci. 104, 10376–10381. https://doi.org/10.1073/pnas.0700962104
Wilson, Z.E., Brimble, M.A., 2008. Molecules derived from the extremes of life. Nat. Prod. Rep. 26, 44–71. https://doi.org/10.1039/B800164M
