Rv2946c (pks1)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: polyketide synthase 1/15
- REFSEQ: polyketide synthase PKS1
- PATRIC: Malonyl CoA-acyl carrier protein transacylase (EC 2.3.1.39)
- TUBERCULIST: Probable polyketide synthase Pks1
- NCBI: Probable polyketide synthase Pks1
- updated information (H37Rv4):
  - gene name: pks1
  - function:
  - reference:
Type: Not Target
Start: 3291503
End: 3296353
Operon:

Trans-membrane region:
Role: I.I - Polyketide and non-ribosomal peptide synthesis
GO terms:
- GO:0071770 - DIM/DIP cell wall layer assembly (Uniprot)
- GO:0071766 - Actinobacterium-type cell wall biogenesis (Uniprot)
- GO:0055114 - oxidation-reduction process (Uniprot)
- GO:0031177 - phosphopantetheine binding (Uniprot)
- GO:0016746 - transferase activity, transferring acyl groups (Uniprot)
- GO:0016740 - transferase activity (Uniprot)
- GO:0016491 - oxidoreductase activity (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:0005886 - plasma membrane (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
6H0J	54%	Mycobacterium ulcerans (strain Agy99)	A1-type ACP domain from module 5 of MLSA1
3SLK	54%	Saccharopolyspora spinosa	Structure of ketoreductase and enoylreductase didomain from modular polyketide synthase
2Z5L	51%	Streptomyces fradiae	The first ketoreductase of the tylosin PKS
6IYO	50%	Streptomyces albus subsp. albus	Crystal Structure of the acyltransferase domain from the second module of the salinomycin polyketide synthase
5HVC	50%	Mycobacterium ulcerans	Solution structure of the apo state of the acyl carrier protein from the MLSA2 subunit of the mycolactone polyketide synthase
5HV8	50%	Mycobacterium ulcerans	Solution structure of an octanoyl- loaded acyl carrier protein domain from module MLSA2 of the mycolactone polyketide synthase.
6OBV	49%	Actinomadura vulgaris	Structural insights into dehydratase substrate selection for the borrelidin and fluvirucin polyketide synthases
6H0Q	49%	Mycobacterium ulcerans (strain Agy99)	B1-type ACP domain from module 7 of MLSB
2JU2	47%	Saccharopolyspora erythraea	Minimized mean solution structure of the acyl carrier protein domain from module 2 of 6-deoxyerythronolide B synthase (DEBS)
5XWV	47%	Streptomyces nodosus	Substrate-bound Structure of a Ketoreductase from the Second Module of the amphotericin Polyketide Synthases

Links to additional information on pks1:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = 0.291 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- BioCyc
- Systems Biology
- Mycobrowser
- PATRIC

Amino Acid Sequence

VISARSAEALTAQAGRLMAHVQANPGLDPIDVGCSLASRSVFEHRAVVVGASREQLIAGLAGLAAGEPGAGVAVGQPGSVGKTVVVFPGQGAQRIGMGRE
LYGELPVFAQAFDAVADELDRHLRLPLRDVIWGADADLLDSTEFAQPALFAVEVASFAVLRDWGVLPDFVMGHSVGELAAAHAAGVLTLADAAMLVVARG
RLMQALPAGGAMVAVAASEDEVEPLLGEGVGIAAINAPESVVISGAQAAANAIADRFAAQGRRVHQLAVSHAFHSPLMEPMLEEFARVAARVQAREPQLG
LVSNVTGELAGPDFGSAQYWVDHVRRPVRFADSARHLQTLGATHFIEAGPGSGLTGSIEQSLAPAEAMVVSMLGKDRPELASALGAAGQVFTTGVPVQWS
AVFAGSGGRRVQLPTYAFQRRRFWETPGADGPADAAGLGLGATEHALLGAVVERPDSDEVVLTGRLSLADQPWLADHVVNGVVLFPGAGFVELVIRAGDE
VGCALIEELVLAAPLVMHPGVGVQVQVVVGAADESGHRAVSVYSRGDQSQGWLLNAEGMLGVAAAETPMDLSVWPPEGAESVDISDGYAQLAERGYAYGP
AFQGLVAIWRRGSELFAEVVAPGEAGVAVDRMGMHPAVLDAVLHALGLAVEKTQASTETRLPFCWRGVSLHAGGAGRVRARFASAGADAISVDVCDATGL
PVLTVRSLVTRPITAEQLRAAVTAAGGASDQGPLEVVWSPISVVSGGANGSAPPAPVSWADFCAGSDGDASVVVWELESAGGQASSVVGSVYAATHTALE
VLQSWLGADRAATLVVLTHGGVGLAGEDISDLAAAAVWGMARSAQAENPGRIVLIDTDAAVDASVLAGVGEPQLLVRGGTVHAPRLSPAPALLALPAAES
AWRLAAGGGGTLEDLVIQPCPEVQAPLQAGQVRVAVAAVGVNFRDVVAALGMYPGQAPPLGAEGAGVVLETGPEVTDLAVGDAVMGFLGGAGPLAVVDQQ
LVTRVPQGWSFAQAAAVPVVFLTAWYGLADLAEIKAGESVLIHAGTGGVGMAAVQLARQWGVEVFVTASRGKWDTLRAMGFDDDHIGDSRTCEFEEKFLA
VTEGRGVDVVLDSLAGEFVDASLRLLVRGGRFLEMGKTDIRDAQEIAANYPGVQYRAFDLSEAGPARMQEMLAEVRELFDTRELHRLPVTTWDVRCAPAA
FRFMSQARHIGKVVLTMPSALADRLADGTVVITGATGAVGGVLARHLVGAYGVRHLVLASRRGDRAEGAAELAADLTEAGAKVQVVACDVADRAAVAGLF
AQLSREYPPVRGVIHAAGVLDDAVITSLTPDRIDTVLRAKVDAAWNLHQATSDLDLSMFALCSSIAATVGSPGQGNYSAANAFLDGLAAHRQAAGLAGIS
LAWGLWEQPGGMTAHLSSRDLARMSRSGLAPMSPAEAVELFDAALAIDHPLAVATLLDRAALDARAQAGALPALFSGLARRPRRRQIDDTGDATSSKSAL
AQRLHGLAADEQLELLVGLVCLQAAAVLGRPSAEDVDPDTEFGDLGFDSLTAVELRNRLKTATGLTLPPTVIFDHPTPTAVAEYVAQQMSGSRPTESGDP
TSQVVEPAAAEVSVHA

(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 50 sites
Non-Essential	Lignoceric Acid	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 50 sites
Non-Essential	Phosphatidylcholine	H37RvMA	Gumbel	Subhalaxmi Nambi	Probability of Essentiality: 0.000000; 3 non-insertions in a row out of 50 sites
Non-Essential	minimal media + 0.1% glycerol	H37RvMA	Gumbel	Griffin et al. (2011)	Probability of Essentiality: 0.000000; 2 non-insertions in a row out of 51 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 51 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: 1.24
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:
- Rv3830c (-) (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:

Property	Value	Creator	Evidence	PMID	Comment
Name	Together with Pks15, type I polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain	mjackson	IMP		Phthiocerol dimycocerosates (PDIM), phenolic glycolipids (PGL) and para-hydroxybenzoic acid derivatives
Citation	Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. P. Constant, E. Perez et al. J. Biol. Chem. 2002	mjackson		12138124	Together with Pks15, type I polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain (phenotypic [mycobacterial recombinant strains])
Other	TBPWY:Phthiocerol dimycocerosates, PGL & pHBAD	mjackson			Together with Pks15, type I polyketide synthase involved in the elongation of p-hydroxybenzoic acid derivatives with malonyl-CoA to form p-hydroxyphenylalkanoates (precursors of phenolic glycolipids [PGL]); the pks15 and pks1 genes are fused in PGL-producing strains of M. tuberculosis but a frameshift mutation causes this polyketide synthase to be inactive in the H37Rv strain (phenotypic [mycobacterial recombinant strains]) P. Constant, E. Perez et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J. Biol. Chem. 2002
Citation	Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. P. Constant, E. Perez et al. J. Biol. Chem. 2002	jjmcfadden		12138124	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay P. Constant, E. Perez et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J. Biol. Chem. 2002

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