Substrate Specificity of 2-Deoxy-<i>scyllo</i>-inosose Synthase, the Starter Enzyme for 2-Deoxystreptamine Biosynthesis, toward Deoxyglucose-6-phosphates and Proposed Mechanism

Abstract

A crucial enzyme in the biosynthesis of the 2-deoxystreptamine aglycon of clinically important aminocyclitol antibiotics is 2-deoxy-scyllo-inosose synthase (DOIS), which is responsible for the initial carbocycle formation of 2-deoxy-scyllo-inosose (1) from D-glucose-6-phosphate (G-6-P) (2). To get more insight into the mechanism and substrate specificity, deoxy-D-glucose-6-phosphates (deoxy-G-6-P) were chemically synthesized and subjected to the reaction with DOIS. The enzyme appeared to use 2-deoxy- and 3-deoxy-G-6-P as substrates, both of which were converted into the corresponding dideoxy-scyllo-inosose products, but 4-deoxy-G-6-P failed in cyclization by DOIS. These results clearly support the proposed reaction mechanism involving the initial oxidation at C-4 of the G-6-P substrate. Another implication is the potential use of DOIS for the preparation of useful dideoxyinososes.