Extremophiles - an innovative source for biactive compounds

Extremophilic organisms are able to survive under hostile environmental conditions like high temperature or elevated UV radiation. This is possible because they develop mechanisms of protection, in most cases by the synthesis of specific metabolites. If respective compounds are able to protect the organisms from harmful conditions, they also might be of relevance for humans. Obvious would be a use in (cosmetic) products, to avoid UV related skin damages. Additionally, respective compounds are also of immense ecological interest. By knowing their structure and quantity, the different defense strategies can be studied and compared. Despite this generally interesting and relevant topic, the majority of algae and cyanobacteria, regardless if the species are of marine or alpine origin, havent been investigated. Little is known about the structure and bioactivity of metabolites that are produced in response to UV stress. In a preceding research project we have already studied some high-altitude algae, and developed protocols for the isolation and analysis of photoprotective compounds. In the current project we will focus primarily on previously not investigated marine species (Antarctic macroalgae, mangrove red algae, etc.) and soil crust algae. All of them are extremophiles and therefore potential sources of new bioactive natural products. It is our aim to select the most interesting species, to isolate, identify and analyze compounds that are induced by UV irradiation, and to study their bioactivity. Accordingly, our efforts combine aspects of biology, pharmacy, chemistry and medicine in a unique way, in order to explore the relevance of so far unstudied extremophiles.

The term extremophile describes organisms, in this project mainly marine algae, that can survive under hostile conditions such as extreme UV radiation. So far, little is known about the metabolites in algae or the corresponding protective mechanisms, although they could also be useful for humans (sun protection). This interdisciplinary research project had the following aims: To characterize the metabolites in so far insufficiently investigated algal species, to study seasonal or geographical variations, to develop a suitable / improved test model for the UV protection of the human skin, and to provide closer insights into the corresponding biological mechanisms of action. A class of UV-protecting substances that often occurs in algae are mycosporine-like amino acids (MAAs). As part of this project, not only could several new representatives be isolated and structurally elucidated (six Bostrychines in Bostrychia scorpiodes, Klebsormidin A and B from Klebsormidium species), but also were analytical methods developed for their quantification and used for chemosystematic studies. It could be shown that in Bostrychia simpliciuscula, for example, four chemotypes can be distinguished, and these results agree to DNA analyzes. Furthermore, it was possible for the first time to determine the stereochemistry of 14 widely found MAAs, for which innovative methods such as ECD (electronic circular dichroism) were used. Other algal constituents also examined or analyzed were bromophenols (in Vertebrata lanosa) and sulfated coumarins in Dasycladus vermicularis. In order to be able to investigate UV-induced changes, a test model based on human skin cells (keratinocytes and fibroblasts) was developed. The formation of reactive oxygen species (ROS) served as indicator. A comparison of the most common chemical UV filters showed an unexpected picture, as some reduced the formation of ROS, others induced it. MAAs were only marginally active in this model. In another study, the effects of the widespread flavonoid kaempferol on human immune cells were examined, and an influence on the tryptophan metabolism was observed for the first time. The complex nature of this project required an interdisciplinary approach, whereby aspects of phytochemistry, analysis, pharmacology and ecology were combined in a unique way. But precisely because of that we have succeeded in gaining a large number of new findings, in a research area that has been little worked on in the past. This is also evidenced by the twelve scientific publications that have emerged from the project so far.