Substrate specificity of 2-deoxy-scyllo-inosose synthase, the starter enzyme for 2-deoxystreptamine biosynthesis, toward deoxyglucose-6-phosphates and proposed mechanism.
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.
Iwase
N
N
Department of Chemistry, Tokyo Institute of Technology, Japan.
Kudo
F
F
Yamauchi
N
N
Kakinuma
K
K
D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D006595:Hexosamines / Q000096:biosynthesis; D007294:Inositol / Q000031:analogs & derivatives* / Q000096:biosynthesis; D008190:Lyases / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D013379:Substrate Specificity