Ribostamycin

Ribostamycin
Clinical data
Other names	(2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-{[(1R,2R,3S,4R,6S)-4,6-diamino-2-{[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy}-3-hydroxycyclohexyl]oxy}oxane-3,4-diol
AHFS/Drugs.com	International Drug Names
ATC code	J01GB10 (WHO) ;
Identifiers
	IUPAC name (1R,2R,3S,4R,6S)-4,6-diamino-3-hydroxy-2-(β-D-ribofuranosyloxy)cyclohexyl 2,6-diamino-2,6-dideoxy-α-D-glucopyranoside;
CAS Number	25546-65-0 ; 53797-35-6 (sulfate);
PubChem CID	33042;
ChemSpider	30581 ;
UNII	2Q5JOU7T53;
ChEMBL	ChEMBL221572 ;
CompTox Dashboard (EPA)	DTXSID6048541 ;
ECHA InfoCard	100.053.421
Chemical and physical data
Formula	C17H34N4O10
Molar mass	454.477 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CN)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O)O)O)N;
	InChI InChI=1S/C17H34N4O10/c18-2-6-10(24)12(26)8(21)16(28-6)30-14-5(20)1-4(19)9(23)15(14)31-17-13(27)11(25)7(3-22)29-17/h4-17,22-27H,1-3,18-21H2/t4-,5+,6-,7-,8-,9+,10-,11-,12-,13-,14-,15-,16-,17+/m1/s1 ; Key:NSKGQURZWSPSBC-VVPCINPTSA-N ;
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Ribostamycin is an aminoglycoside-aminocyclitol antibiotic isolated from a streptomycete, Streptomyces ribosidificus, originally identified in a soil sample from Tsu City of Mie Prefecture in Japan.^[1] It is made up of 3 ring subunits: 2-deoxystreptamine (DOS), neosamine C, and ribose.^[2] Ribostamycin, along with other aminoglycosides with the DOS subunit, is an important broad-spectrum antibiotic with important use against human immunodeficiency virus^{[citation needed]} and is considered a critically important antimicrobial by the World Health Organization.,^[3]^[4] Resistance against aminoglycoside antibiotics, such as ribostamycin, is a growing concern. The resistant bacteria contain enzymes that modify the structure through phosphorylation, adenylation, and acetylation and prevent the antibiotic from being able to interact with the bacterial ribosomal RNAs.^[5]

Biosynthesis

The biosynthesis of ribostamycin begins with the sugar D-glucose, which is phosphorylated at the 6 position to form glucose-6-phosphate. The enzyme rbmA contains a genetic sequence that corresponds to NAD⁺ binding and catalyzes the formation of 2-deoxy-scyllo-inosose. The enzyme rmbB then catalyzes the transamination of 2-deoxy-scyllo-inosose to 2-deoxy-scyllo-inosamine with L-glutamine and pyridoxal phosphate (PLP). Enzyme rbmC oxidizes the ring to 2-deoxy-3-amino-scyllo-inosose, which is then transaminated by enzyme rmbB to DOS. DOS is then glycosylated by the glycosyltransferase rmbD with uridine diphosphate N-acetylglucosamine (UDP-Glc-NAc) to form 2’-N-acetylparomamine. The deacetylase racJ removes the acetyl group and forms paromamine. Paromamine is oxidized by enzyme rbmG and then enzyme rmbH transaminates to produce neamine. Neamine is then ribosylated to form ribostamycin.^[2]^[3]

References

^ Shomura T, Ezaki N, Tsuruoka T, Niwa T, Akita E (March 1970). "Studies on antibiotic SF-733, a new antibiotic. I. Taxonomy, isolation and characterization". The Journal of Antibiotics. 23 (3): 155–61. doi:10.7164/antibiotics.23.155. PMID 5453309.
^ ^a ^b Subba B, Kharel MK, Lee HC, Liou K, Kim BG, Sohng JK (August 2005). "The ribostamycin biosynthetic gene cluster in Streptomyces ribosidificus: comparison with butirosin biosynthesis". Molecules and Cells. 20 (1): 90–6. doi:10.1016/S1016-8478(23)13203-1. PMID 16258246.
^ ^a ^b Kurumbang NP, Liou K, Sohng JK (February 2011). "Biosynthesis of ribostamycin derivatives by reconstitution and heterologous expression of required gene sets". Applied Biochemistry and Biotechnology. 163 (3): 373–82. doi:10.1007/s12010-010-9045-6. PMID 20676801. S2CID 22366703.
^ WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) (2011). Critically Important Antimicrobials for Human Medicine (PDF) (Report) (3rd revision ed.). World Health Organization. ISBN 978-92-4-150448-5.
^ Kudo F, Eguchi T (September 2009). "Biosynthetic genes for aminoglycoside antibiotics". The Journal of Antibiotics. 62 (9): 471–81. doi:10.1038/ja.2009.76. PMID 19644520. S2CID 41969498.

[pmid5453309-1] Shomura T, Ezaki N, Tsuruoka T, Niwa T, Akita E (March 1970). "Studies on antibiotic SF-733, a new antibiotic. I. Taxonomy, isolation and characterization". The Journal of Antibiotics. 23 (3): 155–61. doi:10.7164/antibiotics.23.155. PMID 5453309.

[Subba-2] Subba B, Kharel MK, Lee HC, Liou K, Kim BG, Sohng JK (August 2005). "The ribostamycin biosynthetic gene cluster in Streptomyces ribosidificus: comparison with butirosin biosynthesis". Molecules and Cells. 20 (1): 90–6. doi:10.1016/S1016-8478(23)13203-1. PMID 16258246.

[Kurumbang-3] Kurumbang NP, Liou K, Sohng JK (February 2011). "Biosynthesis of ribostamycin derivatives by reconstitution and heterologous expression of required gene sets". Applied Biochemistry and Biotechnology. 163 (3): 373–82. doi:10.1007/s12010-010-9045-6. PMID 20676801. S2CID 22366703.

[4] WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) (2011). Critically Important Antimicrobials for Human Medicine (PDF) (Report) (3rd revision ed.). World Health Organization. ISBN 978-92-4-150448-5.

[pmid19644520-5] Kudo F, Eguchi T (September 2009). "Biosynthetic genes for aminoglycoside antibiotics". The Journal of Antibiotics. 62 (9): 471–81. doi:10.1038/ja.2009.76. PMID 19644520. S2CID 41969498.

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