ribostamycin
{{short description|Aminoglycoside antibiotic}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 376278091
| 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
| image = Ribostamycin.svg
| tradename =
| Drugs.com = {{drugs.com|international|ribostamycin}}
| pregnancy_AU =
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| protein_bound =
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 25546-65-0
| CAS_supplemental =
{{CAS|53797-35-6}} (sulfate)
| ATC_prefix = J01
| ATC_suffix = GB10
| PubChem = 33042
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 30581
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2Q5JOU7T53
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 221572
| C=17 | H=34 | N=4 | O=10
| 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
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = NSKGQURZWSPSBC-VVPCINPTSA-N
| synonyms = (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-
}}
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.{{cite journal | vauthors = Shomura T, Ezaki N, Tsuruoka T, Niwa T, Akita E | title = Studies on antibiotic SF-733, a new antibiotic. I. Taxonomy, isolation and characterization | journal = The Journal of Antibiotics | volume = 23 | issue = 3 | pages = 155–61 | date = March 1970 | pmid = 5453309 | doi = 10.7164/antibiotics.23.155 | doi-access = free }} It is made up of 3 ring subunits: 2-deoxystreptamine (DOS), neosamine C, and ribose.{{cite journal | vauthors = Subba B, Kharel MK, Lee HC, Liou K, Kim BG, Sohng JK | title = The ribostamycin biosynthetic gene cluster in Streptomyces ribosidificus: comparison with butirosin biosynthesis | journal = Molecules and Cells | volume = 20 | issue = 1 | pages = 90–6 | date = August 2005 | pmid = 16258246 | doi = 10.1016/S1016-8478(23)13203-1| url = | doi-access = free }} Ribostamycin, along with other aminoglycosides with the DOS subunit, is an important broad-spectrum antibiotic with important use against human immunodeficiency virus{{cn|date=February 2022}} and is considered a critically important antimicrobial by the World Health Organization.,{{cite journal | vauthors = Kurumbang NP, Liou K, Sohng JK | title = Biosynthesis of ribostamycin derivatives by reconstitution and heterologous expression of required gene sets | journal = Applied Biochemistry and Biotechnology | volume = 163 | issue = 3 | pages = 373–82 | date = February 2011 | pmid = 20676801 | doi = 10.1007/s12010-010-9045-6 | s2cid = 22366703 }}{{cite report | author = WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance (AGISAR) | publisher = World Health Organization. | title = Critically Important Antimicrobials for Human Medicine | edition = 3rd revision | date = 2011 | url = http://apps.who.int/iris/bitstream/10665/77376/1/9789241504485_eng.pdf | isbn = 978-92-4-150448-5 }} 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.{{cite journal | vauthors = Kudo F, Eguchi T | title = Biosynthetic genes for aminoglycoside antibiotics | journal = The Journal of Antibiotics | volume = 62 | issue = 9 | pages = 471–81 | date = September 2009 | pmid = 19644520 | doi = 10.1038/ja.2009.76 | s2cid = 41969498 | doi-access = free }}
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 {{not a typo|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.
