Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics (contain a high level of microbial resistance) such as the commonly prescribed erythromycin,[1][2] azithromycin, clarithroymcin, methymycin, narbomycin, oleandomycin, picromycin and roxithromycin. As the name suggests, these macrolide antibiotics contain a macrolide or lactone ring and they are attached to the ring desosamine which is crucial for bactericidal activity.[3] The biological action of the desosamine-based macrolide antibiotics is to inhibit the bacterial ribosomal protein synthesis.[4] These antibiotics which contain desosamine are widely used to cure bacterial-causing infections in human respiratory system, skin, muscle tissues, and urethra.
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| Names | |
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| IUPAC name
3,4,6-Trideoxy-3-(dimethylamino)-D-xylo-hexose
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| Systematic IUPAC name
(2R,3S,5R)-3-(Dimethylamino)-2,5-dihydroxyhexanal | |
| Identifiers | |
3D model (JSmol)
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| 2412240 | |
| ChEBI | |
| ChemSpider | |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C8H17NO3 | |
| Molar mass | 175.23 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Discovery
editAlthough desosamine has been found in many macrolide antibiotics, the complete chemical structure of desosamine was not determined until 1962.[5] Nuclear magnetic resonance spectroscopy data was used to establish the complete configuration of desosamine. The hydrogen atoms at the C1,C2,C3, and C5 positions are all found to be axial.[5]
Biosynthesis
editSix enzymes are required for desosamine biosynthesis from TDP-glucose in Streptomyces venezuelae.[1][6] In addition to the required enzymes, there are eight important open reading frames known as the des regions, they are desI~desVIII, these eight frames are the necessary genes used in desosamine biosynthesis, among the 8 des regions, the desI gene implements C-4 Deoxygenation by the enzymatic activity of dehydrase. [7]
Degradation
editDegradation of several of the aforementioned antibiotics yields the desosamine sugar. It is found in combination with the smaller macrolide rings, always attached at C-3 or C-5 of the aglycone. Alkaline degradation found the sugar to be a D-hexose derivative.[8] Glycosidic cleavage of methomycin produces aglycone methynolide and the basic sugar desosamine, whose structure had been determined by oxidative degradation to crotonaldehyde and by other experiments.[9]
Drug resistance
editMacrolide antibiotics that contain desosamine as an amino sugar in their chemical structures sometimes encounter drug-resistant bacteria. The target-site modification can result in changing chemical structure of the antibiotics, for example, a methylation mutation, which will block the drug from normally functioning.[10]
See also
editReferences
edit- ^ a b Rodríguez E, Peirú S, Carney JR, Gramajo H (March 2006). "In vivo characterization of the dTDP-D-desosamine pathway of the megalomicin gene cluster from Micromonospora megalomicea". Microbiology. 152 (Pt 3): 667–673. doi:10.1099/mic.0.28680-0. PMID 16514147.
- ^ Flickinger MC, Perlman D (April 1975). "Microbial degradation of erythromycins A and B". The Journal of Antibiotics. 28 (4): 307–11. doi:10.7164/antibiotics.28.307. PMID 1150530.
- ^ Burgie ES, Holden HM (August 2007). "Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine". Biochemistry. 46 (31): 8999–9006. doi:10.1021/bi700751d. PMC 2528198. PMID 17630700.
- ^ Vázquez-Laslop N, Mankin AS (September 2018). "How Macrolide Antibiotics Work". Trends in Biochemical Sciences. 43 (9): 668–684. doi:10.1016/j.tibs.2018.06.011. PMC 6108949. PMID 30054232.
- ^ a b Woo PW, Dion HW, Durham L, Mosher HS (January 1962). "The stereochemistry of desosamine, an nmr analysis". Tetrahedron Letters. 3 (17): 735–739. doi:10.1016/S0040-4039(00)70510-7.
- ^ Burgie ES, Holden HM (August 2007). "Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine". Biochemistry. 46 (31): 8999–9006. doi:10.1021/bi700751d. PMC 2528198. PMID 17630700.
- ^ Borisova SA, Zhao L, Sherman DH, Liu HW (July 1999). "Biosynthesis of desosamine: construction of a new macrolide carrying a genetically designed sugar moiety". Organic Letters. 1 (1): 133–6. doi:10.1021/ol9906007. PMID 10822548.
- ^ Bolton CH, Foster AB, Stacey M, Webber JM (1961). "Carbohydrate components of antibiotics. Part I. Degradation of desosamine by alkali: Its absolute configuration at position 5". Journal of the Chemical Society. 1961 (4): 4831–4836. doi:10.1039/JR9610004831.
- ^ Berry M (1963). "The macrolide antibiotics". Quarterly Reviews, Chemical Society. 17 (4): 343–361. doi:10.1039/QR9631700343.
- ^ Klugman KP, Lonks JR (June 2005). "Hidden epidemic of macrolide-resistant pneumococci". Emerging Infectious Diseases. 11 (6): 802–7. doi:10.3201/eid1106.050147. PMC 3367596. PMID 15963272.