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MOLECULAR EVOLUTIONARY PATTERNS IN MICROBIAL NATURAL PRODUCT BIOSYNTHETIC GENE AND ENZYME SEQUENCES: SEARCH FOR ADAPTIVE SIGNIFICANCE. H.E. Page¹, C.L. Peterson², and J.V. Lopez². ¹Florida Atlantic University, Boca Raton, and ²Division of Biomedical Marine Research, Harbor Branch Oceanographic Institute, Ft. Pierce.

Understanding gene and protein sequence evolution and their effects on enzymatic structure and function is important for the development of new pharmaceuticals, such as the polyketide class of antibiotics. Results from experiments performed aboard space shuttle flights have clearly indicated that microgravity can provide a beneficial environment for protein growth and presumably drug development. This project employed reverse genetics to study the phenomenon of prokaryotic evolution as an indirect vehicle of drug discovery. Because of their importance, the genes and gene products coding for the biosynthesis of natural products must adapt quickly to environmental pressures. Besides genetic mutation, it is hypothesized that horizontal transfer and positive selection of natural product biosynthetic genes play important roles in microbial evolution, and that significant sequence and structural differences between shallow and deep-water homologues will exist if enzymes of deep-water microbes have had to adjust to increased hydrostatic pressures. These phenomena can be detected by modern molecular methods and inferred based on newly derived and known sequence data. This same logic would be applicable to microbes in a microgravity environment, since they are expected to adapt to a reduced pressure system. To test this hypothesis, new bacterial strains from diverse marine sponges were isolated and inherent polyketide synthase gene fragments were PCR-amplified and cloned. Biosynthetic and housekeeping loci were compared to determine unusual patterns of evolution and infer protein structural differences from shallow versus deep sources.