Rv2948c (fadD22)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: fatty acid CoA ligase FadD22
- REFSEQ: acyl-CoA synthetase
- PATRIC: Long-chain-fatty-acid--CoA ligase FadD22 (EC 6.2.1.3)
- TUBERCULIST: P-hydroxybenzoyl-AMP ligase FadD22
- NCBI: P-hydroxybenzoyl-AMP ligase FadD22
- updated information (H37Rv4):
  - gene name: fadD22
  - function:
  - reference:
Type: Not Target
Start: 3297837
End: 3299954
Operon:

Trans-membrane region:
Role: I.A.3 - Fatty acids
GO terms:
- GO:0097041 - phenolic phthiocerol biosynthetic process (Uniprot)
- GO:0071766 - Actinobacterium-type cell wall biogenesis (Uniprot)
- GO:0044550 - secondary metabolite biosynthetic process (Uniprot)
- GO:0031177 - phosphopantetheine binding (Uniprot)
- GO:0016878 - acid-thiol ligase activity (Uniprot)
- GO:0016874 - ligase activity (Uniprot)
- GO:0009247 - glycolipid biosynthetic process (Uniprot)
- GO:0008610 - lipid biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0006633 - fatty acid biosynthetic process (Uniprot)
- GO:0006631 - fatty acid metabolic process (Uniprot)
- GO:0006629 - lipid metabolic process (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
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:
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
2JU2	44%	Saccharopolyspora erythraea	Minimized mean solution structure of the acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS)
2JU1	44%	Saccharopolyspora erythraea	Solution structure of acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS)
4HKG	37%	Acinetobacter baumannii	Crystal Structure of Free-Standing Peptidyl Carrier Protein from Uncharacterized Acinetobacter baumannii Secondary Metabolic Pathway

Links to additional information on fadD22:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 1.304 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology

Amino Acid Sequence

MRNGNLAGLLAEQASEAGWYDRPAFYAADVVTHGQIHDGAARLGEVLRNRGLSSGDRVLLCLPDSPDLVQLLLACLARGVMAFLANPELHRDDHALAARN
TEPALVVTSDALRDRFQPSRVAEAAELMSEAARVAPGGYEPMGGDALAYATYTSGTTGPPKAAIHRHADPLTFVDAMCRKALRLTPEDTGLCSARMYFAY
GLGNSVWFPLATGGSAVINSAPVTPEAAAILSARFGPSVLYGVPNFFARVIDSCSPDSFRSLRCVVSAGEALELGLAERLMEFFGGIPILDGIGSTEVGQ
TFVSNRVDEWRLGTLGRVLPPYEIRVVAPDGTTAGPGVEGDLWVRGPAIAKGYWNRPDSPVANEGWLDTRDRVCIDSDGWVTYRCRADDTEVIGGVNVDP
REVERLIIEDEAVAEAAVVAVRESTGASTLQAFLVATSGATIDGSVMRDLHRGLLNRLSAFKVPHRFAVVDRLPRTPNGKLVRGALRKQSPTKPIWELSL
TEPGSGVRAQRDDLSASNMTIAGGNDGGATLRERLVALRQERQRLVVDAVCAEAAKMLGEPDPWSVDQDLAFSELGFDSQMTVTLCKRLAAVTGLRLPET
VGWDYGSISGLAQYLEAELAGGHGRLKSAGPVNSGATGLWAIEEQLNKVEELVAVIADGEKQRVADRLRALLGTIAGSEAGLGKLIQAASTPDEIFQLID
SELGK

(Nucleotide sequence available on KEGG)

Additional Information

ESSENTIALITY

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

TnSeqCorr - genes with correlated TnSeq profiles across >100 conditions *new*

Classification	Condition	Strain	Method	Reference	Notes
Non-Essential	Sodium Oleate	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 48 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 48 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 48 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 48 sites
Non-Essential	minimal media + 0.01% cholesterol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 4 non-insertions in a row out of 48 sites
Non-Essential	7H10-glycerol	H37RvMA	TraSH	Sassetti et al. (2003a)
Non-Essential	C57BL/6J mice (8 weeks)	H37RvMA	TraSH	Sassetti et al. (2003b)	Hybridization Ratio: 2.09
Non-Essential	7H09/7H10 + rich media	H37RvMA	MotifHMM	DeJesus et al. (2017)	Fully saturated (14 reps).

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:
- Rv0023 (-) (Direct binding)
- Rv0081 (-) (Direct binding)
- Rv0135c (-) (Direct binding)
- Rv1423 (whiA) (Direct binding)
- Rv2011c (-) (Direct binding)
- Rv3597c (lsr2) (Direct binding)
- Rv0273c (-) (Upstream of operon)

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:

TBCAP

Tubculosis Community Annotation Project (

Slayden et al., 2013

Rv2948c (fadD22)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	Operon Rv2950c	ashwinigbhat	IEP		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Citation	mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009	ashwinigbhat	NAS	19648248	Co-expression (Functional linkage)
Interaction	Operon Rv2949c	ashwinigbhat	NAS		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	Operon Rv2450c	ashwinigbhat	NAS		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Citation	mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009	ashwinigbhat	IEP	19648248	Co-expression (Functional linkage)
Interaction	Regulatory Rv0348	ashwinigbhat	IEP		Co-expression (Functional linkage) B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Interaction	RegulatedBy Rv0348	yamir.moreno	IEP		Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments.. B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009
Name	p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Name	p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates	mjackson	IDA		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Citation	Mycobacterial phenolic glycolipid virulence factor biosynthesis: mechanism and small-molecule inhibition of polyketide chain initiation. JA. Ferreras, KL. Stirrett et al. Chem. Biol. 2008	mjackson		18158259	p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic) JA. Ferreras, KL. Stirrett et al. Mycobacterial phenolic glycolipid virulence factor biosynthesis: mechanism and small-molecule inhibition of polyketide chain initiation. Chem. Biol. 2008
Citation	Cooperation between a coenzyme A-independent stand-alone initiation module and an iterative type I polyketide synthase during synthesis of mycobacterial phenolic glycolipids. W. He,CE. Soll,SS. Chavadi,G. Zhang,JD. Warren,LE. Quadri J. Am. Chem. Soc. 2009	mjackson		19799378	p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic) W. He,CE. Soll,SS. Chavadi,G. Zhang,JD. Warren,LE. Quadri Cooperation between a coenzyme A-independent stand-alone initiation module and an iterative type I polyketide synthase during synthesis of mycobacterial phenolic glycolipids. J. Am. Chem. Soc. 2009
Citation	Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. authors,R. Simone,M. Lger,P. Constant,W. Malaga,H. Marrakchi,M. Daff,C. Guilhot,C. Chalut FEBS J. 2010	mjackson		20553505	p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic) authors,R. Simone,M. Lger,P. Constant,W. Malaga,H. Marrakchi,M. Daff,C. Guilhot,C. Chalut Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 2010

Property

Value

Creator

Evidence

PMID

Comment

Interaction

Operon Rv2950c

ashwinigbhat

IEP

Co-expression (Functional linkage)
B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009

Citation

mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009

ashwinigbhat

NAS

19648248

Co-expression (Functional linkage)

Interaction

Operon Rv2949c

ashwinigbhat

NAS

Co-expression (Functional linkage)
B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009

Interaction

Operon Rv2450c

ashwinigbhat

NAS

Co-expression (Functional linkage)
B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009

Citation

mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. B. Abomoelak, EA. Hoye et al. J. Bacteriol. 2009

ashwinigbhat

IEP

19648248

Co-expression (Functional linkage)

Interaction

Regulatory Rv0348

ashwinigbhat

IEP

Co-expression (Functional linkage)
B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009

Interaction

RegulatedBy Rv0348

yamir.moreno

IEP

Microarrays. mRNA levels of regulated element measured and compared between wild-type and trans-element mutation (knockout, over expression etc.) performed by using microarray (or macroarray) experiments..
B. Abomoelak, EA. Hoye et al. mosR, a novel transcriptional regulator of hypoxia and virulence in Mycobacterium tuberculosis. J. Bacteriol. 2009

Name

mjackson

IMP

Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives

Name

mjackson

IDA

Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives

Citation

Mycobacterial phenolic glycolipid virulence factor biosynthesis: mechanism and small-molecule inhibition of polyketide chain initiation. JA. Ferreras, KL. Stirrett et al. Chem. Biol. 2008

mjackson

18158259

Other

TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD

mjackson

p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
JA. Ferreras, KL. Stirrett et al. Mycobacterial phenolic glycolipid virulence factor biosynthesis: mechanism and small-molecule inhibition of polyketide chain initiation. Chem. Biol. 2008

Citation

Cooperation between a coenzyme A-independent stand-alone initiation module and an iterative type I polyketide synthase during synthesis of mycobacterial phenolic glycolipids. W. He,CE. Soll,SS. Chavadi,G. Zhang,JD. Warren,LE. Quadri J. Am. Chem. Soc. 2009

mjackson

19799378

Other

TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD

mjackson

p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
W. He,CE. Soll,SS. Chavadi,G. Zhang,JD. Warren,LE. Quadri Cooperation between a coenzyme A-independent stand-alone initiation module and an iterative type I polyketide synthase during synthesis of mycobacterial phenolic glycolipids. J. Am. Chem. Soc. 2009

Citation

Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. authors,R. Simone,M. Lger,P. Constant,W. Malaga,H. Marrakchi,M. Daff,C. Guilhot,C. Chalut FEBS J. 2010

mjackson

20553505

Other

TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD

mjackson

p-hydroxybenzoyl-AMP ligase involved in the biosynthesis of phenolic glycolipids; catalyzes the activation of p-hydroxybenzoic acid and its subsequent transfer onto Pks15/1 for the production of p-hydroxyphenylalkanoates (phenotypic [mycobacterial recombinant strains]; enzymatic)
authors,R. Simone,M. Lger,P. Constant,W. Malaga,H. Marrakchi,M. Daff,C. Guilhot,C. Chalut Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 2010

Comments