Neomycin biosynthesis: The incorporation of d-6-deoxy-glucose derivatives and variously labelled glucose into the 2-deoxystreptamine ring: Postulated involvement of 2-deoxyinosose synthase in the biosynthesis

Abstract

d-[6-3H3]6-Deoxy-5-ketoglucose (10) and d-[5,6-3H2]6-deoxyglucose (11) were incorporated into neomycins B and C using a growing culture of Streptomyces fradiae. d-[6-3H]6-Deoxy-5-ketoglucose was incorporated into neomycin, as efficiently as the well established precursor d-glucose, and was found to label exclusively the 2-deoxystreptamine ring of the antibiotic. The results strengthened the previous proposals that in the formation of 2-deoxystreptamine the C-6 hydroxyl group of d-glucose is removed prior to the cyclisation reaction. Studies using the incorporation of d-[3-3H]glucose, d-[3,4-3H2]glucose and d-[5-3H]glucose into neomycin followed by the degradation of the latter established that in the biosynthesis of the 2-deoxystreptamine ring the C-4 and C-5 hydrogen atoms of glucose are removed. The loss of the C-4 hydrogen atom of the glucose is attributed to the formation of a 4-keto derivative which facilitates the removal of the C-5 hydrogen atom thus setting the stage for the expulsion of the C-6 hydroxyl group. The 5,6-olefinic intermediate formed in the process then undergoes cyclisation eventually releasing 2-deoxyinosose. The enzyme systems which participate in the conversion of d-glucose equivalent into 2-deoxyinosose may be described as 2-deoxyinosose synthase that in broad mechanistic terms resembles dehydroquinate synthase. © 1992, JAPAN ANTIBIOTICS RESEARCH ASSOCIATION. All rights reserved.