Optimizing production, isolation, and testing inhibition mechanism of mitochondrial ATPase with Efrapeptin G derived from Tolycludium fungi

Friday, October 28, 2011
Hall 1-2 (San Jose Convention Center)
Natalie Tomaszewski , University of California, Santa Cruz, Santa Cruz
Marjia Draskovic , University of California, Santa Cruz, Santa Cruz
Steve Loveridge , University of California, Santa Cruz, Santa Cruz
Phil Crews, PhD , Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA
Natural products have supplied a variety of compounds that have been tested and designed into drugs to treat diseases. These compounds are often found to be too complex to successfully synthesize in the laboratory, and the microorganisms become the source of their harvest. Testing these compounds against mutant cells sheds light on the mechanism of growth inhibition of tumor and cancer cells. The Tolycludium fungi synthesizes the compound erfapeptin G, a polypeptide that exhibits inhibition of mitochondrial ATPase activity. This compound gives promising results in preventing the growth of tumor and cancer cells. In order to optimize the production of this compound, the growth conditions were adjusted by testing fungal growth in medium with different trace elements. Each trace element was added to different types of media to test which conditions is most efficient for increasing efrapeptin G  production. It was concluded that the  growth of the Tolycludium in Czpedox media with cobalt to allows optimization of efrapeptin G production. Previous studies have suggested efrapeptin inhibition in F1- ATPase interacting with αE, αTP, βE and γ subunits. This experiment is still in progress, yet the anticipated results involve testing this compound against a fungal strain that is mutated in mitochondrial-ATPases, to test the molecular interaction of inhibition between efrapeptin G and mitochondrial-ATPase.