Rv1568 (bioA)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: adenosylmethionine-8-amino-7-oxononanoate aminotransferase
- REFSEQ: adenosylmethionine--8-amino-7-oxononanoate transaminase
- PATRIC: Adenosylmethionine-8-amino-7-oxononanoate aminotransferase (EC 2.6.1.62)
- TUBERCULIST: Adenosylmethionine-8-amino-7-oxononanoate aminotransferase BioA
- NCBI: Adenosylmethionine-8-amino-7-oxononanoate aminotransferase BioA
- updated information (H37Rv4):
  - gene name: bioA
  - function:
  - reference:
Type: Not Target
Start: 1775392
End: 1776705
Operon:

Trans-membrane region:
Role: I.G.1 - Biotin
GO terms:
- GO:0030170 - pyridoxal phosphate binding (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0009102 - biotin biosynthetic process (Uniprot)
- GO:0008483 - transaminase activity (Uniprot)
- GO:0005737 - cytoplasm (Uniprot)
- GO:0004015 - adenosylmethionine-8-amino-7-oxononanoate transaminase activity (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- SAM[c] + 8_AMINO7_OXONOOATE[c] -> 7_8_DIAMINONOOATE[c] + SAM_2_OXOBUTANOATE[c]
Gene Expression Profile (Transcriptional Responses to Drugs; Boshoff et al, 2004)
Gene Modules extracted from cluster analysis of 249 transcriptomic datasets using ICA
Orthologs among selected mycobacteria
Protein structure: 3du4, 3tft, 3tfu, 3drd, 3lv2, 3dod, 3bv0
Search for Homologs in PDB

Top 10 Homologs in PDB (as of Nov 2020):

PDB	aa ident	species	PDB title
6GE8	100%	Mycobacterium tuberculosis	Crystal structure of Mycobacterium tuberculosis BioA
5TE2	100%	Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a mechanism-based inhibitor
5KGT	100%	Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with an inhibitor optimized from HTS lead: 1-[4-[4-(3-chlorophenyl)carbonylpiperidin-1-yl]phenyl]ethanone
5KGS	100%	Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with an inhibitor optimized from HTS lead: 5-[4-(1,3-benzodioxol-5-ylcarbonyl)piperazin-1-yl]-2,3-dihydroinden-1-one
4XJP	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with an inhibitor optimized from HTS lead
4XJO	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with an inhibitor optimized from HTS lead
4XJM	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a HTS lead compound
4XJL	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a HTS lead compound
4XEW	100%	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis, complexed with a HTS lead compound
4WYG	100%	Mycobacterium tuberculosis	Crystal structure of 7,8-diaminopelargonic acid synthase (BioA) from Mycobacterium tuberculosis complexed with a fragment hit

Links to additional information on bioA:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -0.239 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MAAATGGLTPEQIIAVDGAHLWHPYSSIGREAVSPVVAVAAHGAWLTLIRDGQPIEVLDAMSSWWTAIHGHGHPALDQALTTQLRVMNHVMFGGLTHEPA
ARLAKLLVDITPAGLDTVFFSDSGSVSVEVAAKMALQYWRGRGLPGKRRLMTWRGGYHGDTFLAMSICDPHGGMHSLWTDVLAAQVFAPQVPRDYDPAYS
AAFEAQLAQHAGELAAVVVEPVVQGAGGMRFHDPRYLHDLRDICRRYEVLLIFDEIATGFGRTGALFAADHAGVSPDIMCVGKALTGGYLSLAATLCTAD
VAHTISAGAAGALMHGPTFMANPLACAVSVASVELLLGQDWRTRITELAAGLTAGLDTARALPAVTDVRVCGAIGVIECDRPVDLAVATPAALDRGVWLR
PFRNLVYAMPPYICTPAEITQITSAMVEVARLVGSLP

(Nucleotide sequence available on KEGG)

Additional Information

Analysis of Positive Selection in Clinical Isolates new

Analysis of dN/dS (omega) in two collections of Mtb clinical isolates using GenomegaMap (Window model) (see description of methods)
- Moldova: 2,057 clinical isolates
- global set: 5,195 clinical isolates from 15 other countries
In the omega plots, the black line shows the mean estimate of omega (dN/dS) at each codon, and the blue lines are the bounds for the 95% credible interval (95%CI, from MCMC sampling).
A gene is under significant positive selection if the lower-bound of the 95%CI of omega (lower blue line) exceeds 1.0 at any codon.

	Moldova (2,057)	global set (5,195)
under significant positive selection?	NO	NO
omega peak height (95%CI lower bound)	1.34 (0.15)	0.93 (0.3)
codons under selection
omega plots
genetic variants*	link	link
statistics at each codon	link	link

* example format for variants: "D27 (GAC): D27H (CAC,11)" means "Asp27 (native codon GAC) mutated to His (codon CAC) in 11 isolates"

ESSENTIALITY

MtbTnDB - interactive tool for exploring a database of published TnSeq datasets for Mtb

TnSeqCorr - genes with correlated TnSeq profiles across ~100 conditions

Rv1568/bioA, gene len: 1313 bp, num TA sites: 16

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	non-essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	non-essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	essential	BL6 mice	TRASH	essential if hybridization ratio<0.4, min over 4 timepoints (1-8 weeks)
in-vitro (glycerol)	Griffin 2011 PPath	essential	M9 minimal+glycerol	Gumbel	2 replicates; Padj<0.05
in-vitro (cholesterol)	Griffin 2011 PPath	uncertain	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=1.05)	cholesterol vs glycerol	resampling-SR	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in cholesterol
in-vitro	Smith 2022 eLife	growth defect	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	growth defect	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	YES (LFC=-5.058)	in-vivo vs in-vitro	ZINB	YES if Padj<0.05, else not significant; LFC<0 means less insertions/more essential in mice
in-vitro (minimal)	Minato 2019 mSys	essential	minimal medium	HMM
in-vitro (YM rich medium)	Minato 2019 mSys	non-essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	YES (LFC=6.33)	YM rich vs minimal medium	resampling

TnSeq Data No data currently available.

No TnSeq data currently available for this Target.

RNASeq Data No data currently available.

No RNA-Seq data currently available for this Target.

Metabolomic Profiles No data currently available.

No Metabolomic data currently available for this Target.

Proteomic Data No data currently available.

No Proteomic data currently available for this Target.

Regulatory Relationships from Systems Biology

BioCyc

Gene interactions based on ChIPSeq and Transcription Factor Over-Expression (TFOE) (Systems Biology)

NOTE: Green edges represent the connected genes being classified as differentially essential as a result of the middle gene being knocked out. These interactions are inferred based on RNASeq.

Interactions based on ChIPSeq data

Binds To:
- No bindings to other targets were found.
Bound By:

Interactions based on ChIPSeq data (Minch et al. 2014)

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv1353c (-) (Direct binding)

Interactions based on TFOE data (Rustad et al. 2014)

Upregulates:
- Does not upregulate other genes.
Upregulated by:
- Not upregulated by other genes.
Downregulates:
- Does not downregulate other genes.
Downregulated by:

Property	Value	Creator	Evidence	PMID	Comment
Interaction	RegulatedBy Rv3279c	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. G. Balzsi, AP. Heath et al. The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest. Mol. Syst. Biol. 2008
Interaction	RegulatedBy Rv3279c	yamir.moreno	ISO		E.coli orthology based inference. Orthologous pair regulator-target found in E.coli. authors,M. Madan Babu,SA. Teichmann,L. Aravind Evolutionary dynamics of prokaryotic transcriptional regulatory networks. J. Mol. Biol. 2006

TB Genome Annotation Portal