1. 3-Amino-3-deoxy-D-glucose: an antibiotic produced by a deep-sea bacterium
N Fusetani, D Ejima, S Matsunaga, K Hashimoto, K Itagaki, Y Akagi, N Taga, K Suzuki Experientia. 1987 Apr 15;43(4):464-5. doi: 10.1007/BF01940457.
Gram-positive bacteria isolated from deep-sea sediments of the Pacific basin showed considerable antibacterial activity. A Bacillus strain, isolated from a sediment sample collected at a depth of 4310 m, was shown to produce 3-amino-3-deoxy-D-glucose, a known antibiotic.
2. Stepwise Post-glycosylation Modification of Sugar Moieties in Kanamycin Biosynthesis
Fumitaka Kudo, Yukinobu Kitayama, Akimasa Miyanaga, Mario Numakura, Tadashi Eguchi Chembiochem. 2021 May 4;22(9):1668-1675. doi: 10.1002/cbic.202000839. Epub 2021 Feb 11.
Kanamycin A is the major 2-deoxystreptamine (2DOS)-containing aminoglycoside antibiotic produced by Streptomyces kanamyceticus. The 2DOS moiety is linked with 6-amino-6-deoxy-d-glucose (6ADG) at O-4 and 3-amino-3-deoxy-d-glucose at O-6. Because the 6ADG moiety is derived from d-glucosamine (GlcN), deamination at C-2 and introduction of C-6-NH2 are required in the biosynthesis. A dehydrogenase, KanQ, and an aminotransferase, KanB, are presumed to be responsible for the introduction of C-6-NH2 , although the substrates have not been identified. Here, we examined the substrate specificity of KanQ to better understand the biosynthetic pathway. It was found that KanQ oxidized kanamycin C more efficiently than the 3''-deamino derivative. Furthermore, the substrate specificity of an oxygenase, KanJ, that is responsible for deamination at C-2 of the GlcN moiety was examined, and the crystal structure of KanJ was determined. It was found that C-6-NH2 is important for substrate recognition by KanJ. Thus, the modification of the GlcN moiety occurs after pseudo-trisaccharide formation, followed by the introduction of C-6-NH2 by KanQ/KanB and deamination at C-2 by KanJ.
3. The site of inhibition of cell wall synthesis by 3-amino-3-deoxy-D-glucose in Staphylococcus aureus
H Tanaka, S Shimizu, R Oiwa, Y Iwai, S Omura J Biochem. 1979 Jul;86(1):155-9.
The inhibition of growth and cell wall synthesis by 3-amino-3-deoxy-D-glucose (3-AG), which is known to be one of the constituents of the kanamycin molecule and a metabolite of Bacillus sp., was almost completely overcome by glucosamine and N-acetylglucosamine in Staphylococcus aureus but scarcely affected by D-glucose and D-fructose. The antibiotic did not inhibit the incorporation of [14C]glucosamine and [3H]N-acetylglucosamine into the acid-insoluble fraction, but rather enhanced the incorporation of [14C]glucosamine. On the other hand, it inhibited the incorporation of D-[14C]fructose into the cell wall fraction but hardly affected the incorporation of D-[14C]fructose into the acid-insoluble fraction in the presence of pencillin G. Based on these results, it is suggested that the site of primary action of 3-AG is the formation of glucosamine-6-phosphate from D-fructose-6-phosphate, which is catalyzed by glucosamine synthetase [EC 184.108.40.206].