Enzymes
| UniProtKB help_outline | 1 proteins |
| Enzyme class help_outline |
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- Name help_outline neomycin C Identifier CHEBI:65077 Charge 6 Formula C23H52N6O13 InChIKeyhelp_outline PGBHMTALBVVCIT-VZXHOKRSSA-T SMILEShelp_outline [C@H]1([C@H]([C@@H]([C@@H]([NH3+])[C@@H](O[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)O[C@H]3[C@@H]([C@H](C[C@H]([C@@H]3O)[NH3+])[NH3+])O[C@@H]4[C@@H]([C@H]([C@@H]([C@H](O4)C[NH3+])O)O)[NH3+])O1)O)O)C[NH3+] 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-oxoglutarate Identifier CHEBI:16810 (CAS: 64-15-3) help_outline Charge -2 Formula C5H4O5 InChIKeyhelp_outline KPGXRSRHYNQIFN-UHFFFAOYSA-L SMILEShelp_outline [O-]C(=O)CCC(=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 426 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 6'''-deamino-6'''-oxoneomycin C Identifier CHEBI:65068 Charge 5 Formula C23H48N5O14 InChIKeyhelp_outline ISQZALIQHGXYSL-VZXHOKRSSA-S SMILEShelp_outline [NH3+]C[C@H]1O[C@H](O[C@@H]2[C@@H]([NH3+])C[C@@H]([NH3+])[C@H](O)[C@H]2O[C@@H]2O[C@H](CO)[C@@H](O[C@H]3O[C@H](C=O)[C@@H](O)[C@H](O)[C@H]3[NH3+])[C@H]2O)[C@H]([NH3+])[C@@H](O)[C@@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-glutamate Identifier CHEBI:29985 (CAS: 11070-68-1) help_outline Charge -1 Formula C5H8NO4 InChIKeyhelp_outline WHUUTDBJXJRKMK-VKHMYHEASA-M SMILEShelp_outline [NH3+][C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 244 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:33959 | RHEA:33960 | RHEA:33961 | RHEA:33962 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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The oxidoreductases LivQ and NeoQ are responsible for the different 6'-modifications in the aminoglycosides lividomycin and neomycin.
Clausnitzer D., Piepersberg W., Wehmeier U.F.
<h4>Aims</h4>The 2-deoxystreptamine-containing aminoglycoside antibiotics (AGAs) constitute the largest subgroup of the aminoglycosides. Neomycin (NEO) and lividomycin (LIV) are both representatives of the pseudo-tetrasaccharide group among the NEO-type AGAs. While NEO contains a 6'-NH(2) group, t ... >> More
<h4>Aims</h4>The 2-deoxystreptamine-containing aminoglycoside antibiotics (AGAs) constitute the largest subgroup of the aminoglycosides. Neomycin (NEO) and lividomycin (LIV) are both representatives of the pseudo-tetrasaccharide group among the NEO-type AGAs. While NEO contains a 6'-NH(2) group, the 6'-position remains unmodified in LIV. The aim of the study was to characterize the substrate specificities of the enzymes involved in the C-6'- and C-6‴-modification in order to explain the different amination patterns.<h4>Methods and results</h4>We overproduced and purified the enzymes NeoQ (bifunctional 6'- and 6‴-oxidoreductase) and NeoB (bifunctional 6'-and-6‴-aminotransferase), which had been analysed before (Huang et al. 2007), and compared the enzymatic properties with the corresponding enzymes LivQ (postulated 6‴-oxidoreductase, 72% identity to NeoQ) and LivB (postulated 6‴-aminotransferase, 71% identity to NeoB) from the LIV pathway. By applying a newly established photometric assay, we proved that LivQ oxidized only pseudotetrasaccharidic substrates at the 6‴-position. In contrast, NeoQ accepted also the pseudodisaccharidic paromamine as a substrate and oxidized the 6'- and 6‴-positions on two different precursors of NEO. The aminotransferases LivB and NeoB both transfer NH(2) groups to the 6'-position in the precursor 6'-oxo-paromamine and to the 6‴-position of 6‴-oxo-neomycin C.<h4>Conclusions</h4>The difference in the modification pattern of NEO and LIV at their 6'-positions is based only on the difference in the substrate specificities of the oxidoreductases LivQ and NeoQ, respectively. The aminotransferases LivB and NeoB share identical biochemical properties, and both are capable to transaminate the 6' and also the 6‴-position of the tested AGAs.<h4>Significance and impact of the study</h4>Our data provide information to understand the structural variations in aminoglycosides and may be helpful to interpret variations in other natural product bisoynthesis pathways. << Less
J. Appl. Microbiol. 111:642-651(2011) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin.
Huang F., Spiteller D., Koorbanally N.A., Li Y., Llewellyn N.M., Spencer J.B.
The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl:L-glutamate aminotransferase, respectively. The joint activity of Neo-11 and Neo-18 is responsible for the conversi ... >> More
The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl:L-glutamate aminotransferase, respectively. The joint activity of Neo-11 and Neo-18 is responsible for the conversion of paromamine to neamine in the biosynthetic pathway of neomycin through a mechanism of FAD-dependent dehydrogenation followed by a pyridoxal-5'-phosphate-mediated transamination. Neo-18 is also shown to catalyze deamination at C-6''' of neomycin, thus suggesting bifunctional roles of the two enzymes in the formation of both neosamine rings of neomycin. The product of the btrB gene, a homologue of neo-18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans, exhibits the same activity as Neo-18; this indicates that there is a similar reaction sequence in both butirosin and neomycin biosynthesis. << Less
ChemBioChem 8:283-288(2007) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation.
Park J.W., Park S.R., Nepal K.K., Han A.R., Ban Y.H., Yoo Y.J., Kim E.J., Kim E.M., Kim D., Sohng J.K., Yoon Y.J.
Kanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pa ... >> More
Kanamycin is one of the most widely used antibiotics, yet its biosynthetic pathway remains unclear. Current proposals suggest that the kanamycin biosynthetic products are linearly related via single enzymatic transformations. To explore this system, we have reconstructed the entire biosynthetic pathway through the heterologous expression of combinations of putative biosynthetic genes from Streptomyces kanamyceticus in the non-aminoglycoside-producing Streptomyces venezuelae. Unexpectedly, we discovered that the biosynthetic pathway contains an early branch point, governed by the substrate promiscuity of a glycosyltransferase, that leads to the formation of two parallel pathways in which early intermediates are further modified. Glycosyltransferase exchange can alter flux through these two parallel pathways, and the addition of other biosynthetic enzymes can be used to synthesize known and new highly active antibiotics. These results complete our understanding of kanamycin biosynthesis and demonstrate the potential of pathway engineering for direct in vivo production of clinically useful antibiotics and more robust aminoglycosides. << Less
Nat. Chem. Biol. 7:843-852(2011) [PubMed] [EuropePMC]
This publication is cited by 13 other entries.