Microbiology and Biochemistry of Secondary Metabolites Unit (Holger Jenke-Kodama)
Assistant Professor Dr. Holger Jenke-Kodama
holger.jenke-kodama at oist.jp
The Microbiology and Biochemistry of Secondary Metabolites Unit works on natural products that are biosynthesised by microorganisms. Secondary metabolites are small compounds that belong to diverse chemical substance classes and show a taxonomically inhomogeneous distribution. Many of these substances have pharmaceutically important bioactivities like antiobiotic, cytotoxic and antifungal activities, and some of them are classified as toxins. The last years, however, have seen an increasing interest in the biological functions of those compounds.
From an evolutionary perspective, the key questions are: How is the plethora of compounds created, and how does natural selection influence secondary metabolism? To answer these questions we need information about the chemical structures of metabolites, biosynthesis schemes, gene cluster organisation and gene expression patterns. To understand the evolution of secondary metabolite pathways we need to combine the data at the systems level using both experimental and computational approaches. Furthermore, we are interested in biotechnological applications of those compounds.
Currently, the unit is working on bacterial model organisms, toxin producing dinoflagellates and environmental microbial communities that are associated to marine invertebrates. Moreover, we are studying a green microalgal species in order to improve its biotechnological potential as a biofuel source. The latter topic mirrors one important objective of OIST, namely to combine basic research and applied approaches in order to work also on the development of new technologies.
One focus of our research is on modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs). These are multienzyme systems of bacterial secondary metabolism that perform a stepwise biosynthesis in an assembly line-like fashion. Many polyketides and nonribosomally made peptides possess interesting bioactivities like antibiotic, antifungal and cytotoxic activities. Besides, some of them have been reported to play important roles in the physiology of the producing organisms. Biochemical, genetic and evolutionary studies have revealed the mechanisms underlying the enormous structural diversity produced by PKSs and NRPSs. Organisms seem to use secondary metabolism like a laboratory or “chemical playground” in order to provide various structures, which are mostly lost over time, but are preserved when they have been acquired to perform a specific function. Knowledge about this fixation process is still scarce. Since this process has to be accompanied by both the development of suitable regulation patterns and integration into the existing regulatory network, a systems biology-related approach is the best way to gain new insights. Systems biology is aimed at an integrated understanding of life forms at multiple levels. Evolutionary systems biology focuses on the ways biological systems change over time. Combining reconstructed metabolic networks, gene expression data, phylogenomics and comparative genomics will provide a deeper understanding of the evolutionary dynamics of secondary metabolism.