Biosynthetic pahway
editFirst isolated from the Streptomyces fradiae and Streptomyces albogriseus in 1949 (NBRC 12773).[1] Neomycin is a mixture of neomycin B (framycetin); and its epimer neomycin C, the latter component accounting for some 5–15% of the mixture. Neomycin has good activity against Gram-positive and Gram-negative bacteria, but is very ototoxic. Its use is thus restricted to oral treatment of intestinal infections.[2]
Neomycin B is composed of four parts: D-neosamine, 2-deoxystreptamine (2-DOS), D-ribose, and L-neosamine. Neomycin A, also called neamine, contains D-neosamine and 2-deoxystreptamine. Neamine is made from six genes, DOIS gene (btrC, neo7); L-glutamine:DOI aminotransferase gene (btrS, neo6); a putative glycosyltransferase gene (btrM, neo8); a putative aminotransferase (similar to glutamate-1-semialdehyde 2,1- aminomutase) gene (btrB, neo18); a putative alcohol dehydrogenase gene (btrE, neo5); another putative dehydrogenase (similar to chorine dehydrogenase and related flavoproteins) gene (btrQ, neo11).[3] A deacetylase acting to remove the acetyl group on N-acetylglucosamine moieties of aminoglycoside intermediates (Neo16), still needs to be clarified (sequence similar to BtrD).[4]
Next is the attachment of the D-ribose via ribosylation of neamine, using 5-phosphoribosyl-1-diphosphate (PRPP) as the ribosyl donor (BtrL, BtrP);[5] glycosyltransferase (potential homologues RibF, LivF, Parf) gene (Neo15).[6]
Neosamine B (L-neosamine B) is most likely biosynthesized in the same manner as the neosamine C (D-niosamine) in neamine biosynthesis, but with an additional epimerization step required to account for the presence of the epimeric neosamine B in neomycin B.[7]
Notes
edit- ^ Selman A., Waksman (September 1, 1949). "Neomycin-production and antibiotic properties". Journal of Clinical Investigation. 28 (5): 934. Retrieved May 21, 2016.
- ^ Dewick M., Dewick (March 2009). Dr (3rd ed.). The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom (Page 4).: John Wiley and Sons Ltd. pp. 508, 510, 511. ISBN 978-0-470-74168-9.
{{cite book}}:|access-date=requires|url=(help)CS1 maint: location (link) - ^ Kudo, Fumitaka (November 20, 2005). "Biosynthesis of 2-Deoxystreptamine by Three Crucial Enzymes in Streptomyces fradiae NBRC 12773" (PDF). Journal of Antibiotics. 58 (12): 766–774. Retrieved May 12, 2016.
- ^ Won Park, Je (October 9, 2011). "Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation". Nature Chemical Biology. 7: 843–850.
- ^ Kudo, Fumitaka (April 20, 2007). "Unique O-ribosylation in the biosynthesis of butirosin" (PDF). Bioorganic & Medicinal Chemistry. 15 (13): 4360–4362. Retrieved May 12, 2016.
- ^ Spencer B., Jonathan (June 20, 2008). "The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase". Organic and Bimolecular Chemistry. 6 (18): 3307. Retrieved May 21, 2016.
- ^ Llewellyn M., Nicholas; Spencer B., Jonathan (September 25, 2006). "Biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics". Natural Products Reports. 23. Retrieved May 23, 2016.