Biosynthesis and reactivity of a novel antibiotic: Abyssomicin C

CHED 785

C. Stieber, stiebesc@whitman.edu1, E. Gottardi2, and RD. Süssmuth2. (1) Department of Chemistry, Whitman College, 280 Boyer Ave., Walla Walla, WA 99362, (2) Institut für Chemie, Technische Universität Berlin, Berlin, Germany
The emergence of new mechanisms of antibiotic drug resistance against many effective antibiotics has led to the search for new classes of antibiotics. In 2004, the Abyssomicins were purified from the marine Verrucosispora strain AB-18-032. Of the three Abyssomicins (B, C, D), only C was found to have antibiotic potential, as it inhibits gram-positive bacteria. Because Abyssomicin C has a very unique structure, we are particularly interested in its biosynthesis. Most of the gene cluster was previously sequenced and it was determined that Abyssomicin C is synthesized by Polyketide Synthases (PKS). This study continued the elucidation of the gene cluster responsible for Abyssomicin C, and the determination as to which genes are necessary for the production of Abyssomicin C. It is known that Abyssomicin C inhibits the folic acid biosynthesis pathway between chorismate and para-aminobenzoic acid (pABA), although the mechanism of inactivation is unclear. For this reason, reactivity studies of Abyssomicin C with various amino acids were performed.