The sulfur-containing antibiotic BE-7585A: A study of its synthesis

Abstract

Antibiotics are often differentiated and divided using two classes, grouped by function and structure. The molecular basis and mechanism of action of many antibiotics have been studied and identified through recent advancements in molecular biology. The main structural feature of BE-7585A is an angucycline ring. Antibiotics with this unique ring structure are known to have diverse biological functions such as antitumor, enzyme inhibitory, and blood platelet aggregation inhibitory activity [1]. Although the biological effects of BE-7585A have not been studied in detail, similar synthetic pathways have begun to be elucidated, such as urdamycin and aquayamycin by the Rohr Group [2]. However, unlike urdamycin, BE-7585A has a unique feature. It is one of few naturally occurring compounds containing a C-2 thiosugar. The incorporation of this sulfur moiety in this compound, or any other C-2 thiosugar compounds, has never been studied. Two main experiments were carried out in this work to study and elucidate part of the biosynthetic pathway of this C-2 thiosugar formation. First, a pull-down assay was performed to find the sulfur donor critical to the pathway. Second, kinetic studies of the 2-thio-trehalose-6-phosphate synthase were done to determine the km and vmax values. Although the results of the first experiment were found to be inconclusive, the kinetic parameters of the reaction catalyzed by the 2-thio-trehalose-6-phosphate synthase were determined.