With this award, the Chemistry of Life Processes Program is supporting an International Collaboration in Chemistry (ICC) collaborative between Professors David H. Sherman of the University of Michigan and Roberto G. S. Berlinck of the Universidade de Sao Paulo, Brazil (supported by the Sao Paulo Research Foundation (FAPESP)). The objective of this research effort is to investigate fundamental aspects of alkaloid natural product assembly and tailoring by marine fungi derived from Brazilian biodiversity resources. The fungal alkaloid natural products are among the most under-explored from a genetic and biochemical point of view. The University of Michigan will conduct total genome sequencing, bioinformatic mining, and annotation to identify target natural product biosynthetic systems from selected marine fungi. Molecular genetic and biochemical approaches will be employed collaboratively to understand the basis for construction of the core polycyclic ring systems, as well as oxidative modifications and structural rearrangements to elaborate the complex suÃte of molecules within this fascinating class of metabolites. The group in Brazil will work on manipulating growth condition to maximize production of key biosynthetic intermediates and final products to facilitate an understanding of fundamental genetic and physiological factors involved in augmenting secondary metabolism and output of natural products.
The mechanisms for creating chemical diversity in these pathways are often unique compared to bacterial and plant systems. Thus, there are great opportunities to gain new knowledge that can lead to pathway engineering and advance the fields of chemical biology and medicinal chemistry. The Broader Impacts of the proposal are multi-factorial and include expanding the genomic and biochemical basis for fungal alkaloid natural product diversification and training of students and postdoctoral fellows in cross-disciplinary aspects of natural product sciences. The PI at the University of Michigan plans to conduct workshops in Brazil to promote training in natural product pathway engineering and synthetic biology applications.
