Postdoctoral Fellowship in Biology FY 2019: The Diversity of a New Carbon-Activating Halogenase from Cyanobacteria

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2019, Research Using Biological Collections. The fellowship supports research and training of the fellow that will utilize biological collections in innovative ways. Photosynthetic bacteria known as cyanobacteria produce a variety of organic molecules with unusual chemical structures, including halogenated molecules, which contain chlorine and bromine and are produced using enzymes called halogenases. The enzymes are unusual because they can form chemical bonds at carbon atoms that other enzymes cannot use. A better understanding of halogenases will lead to new insights in chemistry. Towards that goal, the fellow will study a newly discovered type of halogenase that is able to attach halogen atoms to molecules called fatty acids. This project will lay the groundwork for understanding a new type of carbon-activating enzyme, with applications for the development of new synthetic methods in chemistry to produce industrially important molecules. The fellow will engage in public outreach, including interactive museum exhibits, to highlight the importance of microbiology in every-day human life.<br/><br/>In an international collaboration with the University of Porto, Portugal, this research will use DNA sequence data to identify new halogenases from the LEGE collection of cyanobacteria. Using a PCR-based approach, the fellow will identify LEGE strains that contain homologs of a fatty acid halogenase, with follow-up validation by whole genome sequencing. The fellow will clone, heterologously express, purify, and functionally characterize the new homologs from the LEGE collection, in addition to homologs from other culture collections, to identify genetic determinants of enzyme selectivity and explore the relationships between evolution and enzyme activity. The fellow will also use liquid chromatography and mass spectrometry to identify new halogenated compounds produced by species in the LEGE collection. The fellow will isolate and structurally characterize these compounds with the goal of connecting new halogenase-containing biosynthetic gene clusters to the molecules they produce. By characterizing the functional and genetic diversity of fatty acid halogenases in cyanobacteria, this work will document the utility of new halogenases for carbon activation in chemical synthesis. In performing this research, the fellow will receive training in bioinformatics, chemical synthesis, and natural products isolation and characterization. This research will be performed with assistance from undergraduates, whom the fellow will train and mentor, and it will build new collaborations for the analysis of interdisciplinary datasets in chemistry and biology.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.