Molecule Information

General Information of the Molecule (ID: Mol01993)

• Name: FO synthase (FBIC) ,Mycobacterium tuberculosis
• Synonyms: fbiC; Rv1173
• Molecule Type: Protein
• Gene Name: FBIC
• Gene ID: 886061
• Sequence:
  MPQPVGRKSTALPSPVVPPQANASALRRVLRRARDGVTLNVDEAAIAMTARGDELADLCA
  SAARVRDAGLVSAGRHGPSGRLAISYSRKVFIPVTRLCRDNCHYCTFVTVPGKLRAQGSS
  TYMEPDEILDVARRGAEFGCKEALFTLGDRPEARWRQAREWLGERGYDSTLSYVRAMAIR
  VLEQTGLLPHLNPGVMSWSEMSRLKPVAPSMGMMLETTSRRLFETKGLAHYGSPDKDPAV
  RLRVLTDAGRLSIPFTTGLLVGIGETLSERADTLHAIRKSHKEFGHIQEVIVQNFRAKEH
  TAMAAFPDAGIEDYLATVAVARLVLGPGMRIQAPPNLVSGDECRALVGAGVDDWGGVSPL
  TPDHVNPERPWPALDELAAVTAEAGYDMVQRLTAQPKYVQAGAAWIDPRVRGHVVALADP
  ATGLARDVNPVGMPWQEPDDVASWGRVDLGAAIDTQGRNTAVRSDLASAFGDWESIREQV
  HELAVRAPERIDTDVLAALRSAERAPAGCTDGEYLALATADGPALEAVAALADSLRRDVV
  GDEVTFVVNRNINFTNICYTGCRFCAFAQRKGDADAYSLSVGEVADRAWEAHVAGATEVC
  MQGGIDPELPVTGYADLVRAVKARVPSMHVHAFSPMEIANGVTKSGLSIREWLIGLREAG
  LDTIPGTAAEILDDEVRWVLTKGKLPTSLWIEIVTTAHEVGLRSSSTMMYGHVDSPRHWV
  AHLNVLRDIQDRTGGFTEFVPLPFVHQNSPLYLAGAARPGPSHRDNRAVHALARIMLHGR
  ISHIQTSWVKLGVRRTQVMLEGGANDLGGTLMEETISRMAGSEHGSAKTVAELVAIAEGI
  GRPARQRTTTYALLAA
• Function: Catalyzes the radical-mediated synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) from 5-amino-6-(D-ribitylamino)uracil and L-tyrosine.
• Uniprot ID: FBIC_MYCTU

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: 85007
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Delamanid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Tuberculosis [ICD-11: 1B10.0] [1]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Resistant Drug: Delamanid
• Molecule Alteration: Mutation; Q79K
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6] [2]

• Resistant Disease: Mycolicibacterium smegmatis infection [ICD-11: 1B2Z.6]
• Resistant Drug: Delamanid
• Molecule Alteration: Missense mutation; p.V318I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain; 1313
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: alamarBlue assay
• Mechanism Description: Mutation in codon 318 of the fbiC gene was identified as the sole mutation related to DMD resistance.

References

• Ref 1: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.
• Ref 2: In Vitro Drug Susceptibility of Bedaquiline, Delamanid, Linezolid, Clofazimine, Moxifloxacin, and Gatifloxacin against Extensively Drug-Resistant Tuberculosis in Beijing, China .Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00900-17. doi: 10.1128/AAC.00900-17. Print 2017 Oct. 10.1128/AAC.00900-17