Nourseothricin

n=1-4
Names
IUPAC name
[(2R,3S,4R,5R,6R)-6-[[(3aS,7R,7aS)-7-hydroxy-4-oxo-1,3a,5,6,7,7a-hexahydroimidazo[4,5-c]pyridin-2-yl]amino]-5-[[(3S)-3,6-diaminohexanoyl]amino]-4-hydroxy-2-(hydroxymethyl)oxan-3-yl] carbamate
Identifiers
3D model (JSmol)
ChEMBL
  • InChI=1S/C19H34N8O8/c20-3-1-2-7(21)4-10(30)24-13-14(31)15(35-18(22)33)9(6-28)34-17(13)27-19-25-11-8(29)5-23-16(32)12(11)26-19/h7-9,11-15,17,28-29,31H,1-6,20-21H2,(H2,22,33)(H,23,32)(H,24,30)(H2,25,26,27)/t7-,8+,9+,11+,12-,13+,14+,15+,17+/m0/s1
    Key: NRAUADCLPJTGSF-ZPGVOIKOSA-N
  • C1[C@H]([C@@H]2[C@@H](C(=O)N1)N=C(N2)N[C@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)OC(=O)N)O)NC(=O)C[C@H](CCCN)N)O
Properties
C19H34N8O8
Molar mass 502.529 g·mol−1
~ 1 g/L
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Nourseothricin (NTC) is a member of the streptothricin-class of aminoglycoside antibiotics produced by Streptomyces species. Chemically, NTC is a mixture of the related compounds streptothricin C, D, E, and F.[1] NTC inhibits protein synthesis by inducing miscoding. It is used as a selection marker for a wide range of organisms including bacteria, yeast, filamentous fungi, and plant cells. It is not known to have adverse side-effects on positively selected cells, a property cardinal to a selection drug.[2]

Streptothricin F is effective against highly drug-resistant gram-negative bacteria, including carbapenem-resistant E. coli.[3]

NTC can be inactivated by nourseothricin N-acetyl transferase (NAT) from Streptomyces noursei, an enzyme that acetylates the beta-amino group of the beta-lysine residue of NTC.[4] NAT can thus act as an antibiotic resistance gene.[5]

Properties

NTC is highly soluble in water (~ 1 g/mL) and stable in solution for 2 years at 4 °C.[6]

References

  1. ^ "Nourseothricin" (PDF).
  2. ^ Kochupurakkal BS, Iglehart JD (2013). "Nourseothricin N-acetyl transferase: a positive selection marker for mammalian cells". PLOS ONE. 8 (7): e68509. Bibcode:2013PLoSO...868509K. doi:10.1371/journal.pone.0068509. PMC 3701686. PMID 23861913.
  3. ^ Morgan, Christopher E.; Kang, Yoon-Suk; Green, Alex B.; Smith, Kenneth P.; Dowgiallo, Matthew G.; Miller, Brandon C.; Chiaraviglio, Lucius; Truelson, Katherine A.; Zulauf, Katelyn E.; Rodriguez, Shade; Kang, Anthony D.; Manetsch, Roman; Yu, Edward W.; Kirby, James E. (2023-05-16). "Streptothricin F is a bactericidal antibiotic effective against highly drug-resistant gram-negative bacteria that interacts with the 30S subunit of the 70S ribosome". PLOS Biology. 21 (5): e3002091. doi:10.1371/journal.pbio.3002091. ISSN 1545-7885. PMC 10187937. PMID 37192172.
  4. ^ Krügel H, Fiedler G, Smith C, Baumberg S (1993). "Sequence and transcriptional analysis of the nourseothricin acetyltransferase-encoding gene nat1 from Streptomyces noursei". Gene. 127 (1): 127–31. doi:10.1016/0378-1119(93)90627-f. PMID 8486278.
  5. ^ Shen J, Guo W, Köhler JR (2005). "CaNAT1, a heterologous dominant selectable marker for transformation of Candida albicans and other pathogenic Candida species". Infection and Immunity. 73 (2): 1239–42. doi:10.1128/IAI.73.2.1239-1242.2005. PMC 547112. PMID 1566497. S2CID 37895453.
  6. ^ NTC properties, Jena Bioscience


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