Ribostamycin is an

aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...

-aminocyclitol antibiotic isolated from a streptomycete, ''Streptomyces ribosidificus'', originally identified in a soil sample from Tsu City of Mie Prefecture in Japan. It is made up of 3 ring subunits: 2-deoxystreptamine (DOS), neosamine C, and

ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally occurring form, , is a component of the ribonucleotides from which RNA is built, and so this comp ...

. Ribostamycin, along with other aminoglycosides with the DOS subunit, is an important broad-spectrum antibiotic with important use against human immunodeficiency virus and is considered a critically important antimicrobial by the

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

., 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 RNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal ...

Biosynthesis

The biosynthesis of ribostamycin begins with the sugar D-glucose, which is phosphorylated at the 6 position to form

glucose-6-phosphate Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this wa ...

. 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 Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependen ...

(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 Uridine diphosphate ''N''-acetylglucosamine or UDP-GlcNAc is a nucleotide sugar and a coenzyme in metabolism. It is used by glycosyltransferases to transfer ''N''-acetylglucosamine residues to substrates. UDP-GlcNAc is used for making glycosami ...

(UDP-Glc-NAc) to form 2’-''N''-acetylparomamine. The deacetylase 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. : Ribostamycin Proposedbiosynthesis

References

{{AminoglycosideAntiBiotics Aminoglycoside antibiotics