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.
1992; Springer Nature; Volume: 45; Issue: 6 Linguagem: Inglês
10.7164/antibiotics.45.984
ISSN1881-1469
AutoresSAVED K. GODA, Muhammad Akhtar,
Tópico(s)Amino Acid Enzymes and Metabolism
ResumoD-[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 G-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.
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