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Pathway Description
Neotrehalosadiamine biosynthesis: ntdA, ntdB, ntdC
Bacillus subtilis (strain 168)
Category:
Metabolite Pathway
Sub-Category:
Signaling
Created: 2025-03-25
Last Updated: 2025-07-31
The regulation of the ntdABC operon. The operon is activated by ntdR (NTD biosynthesis operon regulator) and neotrehalosadiamine. The operon is inhibited by glcP (Glucose/mannose transporter). NtdR is required for the proper function of crp in transcription of the operon and ntdR cannot bind to the promoter without neotrehalosadiamine. GlcP controls the amount of glucose that is present inside the cell (acts as a glucose sensor), therefore, it indirectly inhibits ntdR function. There are three products from this operon: ntdA (3-oxo-glucose-6-phosphate:glutamate aminotransferase), ntdB (Kanosamine-6-phosphate phosphatase) and ntdC (Glucose-6-phosphate 3-dehydrogenase). These products are all enzymes used in the biosynthesis of neotrehalosadiamine from glucose. NtdC is used to turn D-glucose-6-phosphate (imported into the cell by ptsG: PTS system glucose-specific EIICBA component) to 3-dehydro-D-glucose-6-phosphate. NtdA is used to turn 3-dehydro-D-glucose-6-phosphate to D-kanosamine-6-phosphate. NtdB is used to turn D-kanosamine-6-phosphate to kanosamine. The process of kanosamine to neotrehalosadiamine is unknown.
References
Neotrehalosadiamine biosynthesis: ntdA, ntdB, ntdC References
Saito N, Nguyen HM, Inaoka T: Impact of activation of neotrehalosadiamine/kanosamine biosynthetic pathway on the metabolism of Bacillus subtilis. J Bacteriol. 2021 May 1;203(9):e00603-20. doi: 10.1128/JB.00603-20. Epub 2021 Feb 22.
Pubmed: 33619155
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Pubmed: 5566979
van Straaten KE, Ko JB, Jagdhane R, Anjum S, Palmer DRJ, Sanders DAR: The structure of NtdA, a sugar aminotransferase involved in the kanosamine biosynthetic pathway in Bacillus subtilis, reveals a new subclass of aminotransferases. J Biol Chem. 2013 Nov 22;288(47):34121-34130. doi: 10.1074/jbc.M113.500637. Epub 2013 Oct 4.
Pubmed: 24097983
Inaoka T, Takahashi K, Yada H, Yoshida M, Ochi K: RNA polymerase mutation activates the production of a dormant antibiotic 3,3'-neotrehalosadiamine via an autoinduction mechanism in Bacillus subtilis. J Biol Chem. 2004 Jan 30;279(5):3885-92. doi: 10.1074/jbc.M309925200. Epub 2003 Nov 11.
Pubmed: 14612444
Cossart P, Gicquel-Sanzey B: Cloning and sequence of the crp gene of Escherichia coli K 12. Nucleic Acids Res. 1982 Feb 25;10(4):1363-78. doi: 10.1093/nar/10.4.1363.
Pubmed: 6280141
Aiba H, Fujimoto S, Ozaki N: Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. Nucleic Acids Res. 1982 Feb 25;10(4):1345-61. doi: 10.1093/nar/10.4.1345.
Pubmed: 6280140
Blattner FR, Plunkett G 3rd, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, Gregor J, Davis NW, Kirkpatrick HA, Goeden MA, Rose DJ, Mau B, Shao Y: The complete genome sequence of Escherichia coli K-12. Science. 1997 Sep 5;277(5331):1453-62. doi: 10.1126/science.277.5331.1453.
Pubmed: 9278503
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