Rv3800c (pks13)

Current annotations:
- TBCAP: (community-based annotations - see table at bottom of page)
- TBDB: polyketide synthase 13
- REFSEQ: polyketide synthase PKS13
- PATRIC: Probable polyketide synthase similar to many. e.g. gp|M63676|SERERYAA_1 S.erythraea first ORF of eryA gene involved in complex polyketide formation in erythromycin biosynthesis.
- TUBERCULIST: Polyketide synthase Pks13
- NCBI: Polyketide synthase Pks13
- updated information (H37Rv4):
  - gene name: pks13
  - function:
  - reference:
Type: Not Target
Start: 4255945
End: 4261146
Operon:

Trans-membrane region:
Role: I.I - Polyketide and non-ribosomal peptide synthesis
GO terms:
- GO:0031177 - phosphopantetheine binding (Uniprot)
- GO:0016788 - hydrolase activity, acting on ester bonds (Uniprot)
- GO:0009058 - biosynthetic process (Uniprot)
- GO:0008152 - metabolic process (Uniprot)
- GO:0003824 - catalytic activity (Uniprot)
Reaction(s) (based on iSM810 metabolic model):
- HEXACOSANOYL_COA_CO2[c] + MEROACYL_AMP[c] -> CO2[c] + COA[c] + AMP[c] + C78_3_OXY_MYCOLATE_ENZ[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: 3tzw, 3tzx, 3tzy, 3tzz
Search for Homologs in PDB

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

PDB	aa ident	species	PDB title
6D8J	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis polyketide synthase 13 N-terminal acyl carrier protein domain
6D8I	100%	Mycobacterium tuberculosis	Mycobacterium tuberculosis polyketide synthase 13 N-terminal acyl carrier protein domain
6C4Q	100%	Mycobacterium tuberculosis	1.16 Angstrom Resolution Crystal Structure of Acyl Carrier Protein Domain (residues 1-100) of Polyketide Synthase Pks13 from Mycobacterium tuberculosis
5XUO	100%	Mycobacterium tuberculosis H37Rv	Pks13 AT domain fragment from Mycobacterium tuberculosis
5V42	100%	Mycobacterium tuberculosis	Crystal Structure of Mtb Pks13 Thioesterase domain in complex with inhibitor TAM3
5V41	100%	Mycobacterium tuberculosis	Crystal Structure of Mtb Pks13 Thioesterase domain in complex with inhibitor TAM5
5V40	100%	Mycobacterium tuberculosis	Crystal Structure of Mtb Pks13 Thioesterase domain in complex with inhibitor TAM6
5V3Y	100%	Mycobacterium tuberculosis	Crystal Structure of Mtb Pks13 Thioesterase domain in complex with inhibitor TAM16
5V3X	100%	Mycobacterium tuberculosis	Crystal Structure of Mtb Pks13 Thioesterase domain in complex with inhibitor TAM1
5V3W	100%	Mycobacterium tuberculosis	Crystal Structure of the Apo form of Thioesterase domain of Mtb Pks13

Links to additional information on pks13:
- TBDB (updated)
- Phyre2 structure prediction, model: final.casp.pdb (from Mao et al, 2013)
- UniProt
- AlphaFold model
- Vulnerability = -9.055 (from Jeremy Rock's lab)
- KEGG - nucleotide and amino acid sequences of gene
- Mycobrowser
- PATRIC
- BioCyc
- Systems Biology
- Photo of spot titer

Amino Acid Sequence

MADVAESQENAPAERAELTVPEMRQWLRNWVGKAVGKAPDSIDESVPMVELGLSSRDAVAMAADIEDLTGVTLSVAVAFAHPTIESLATRIIEGEPETDL
AGDDAEDWSRTGPAERVDIAIVGLSTRFPGEMNTPEQTWQALLEGRDGITDLPDGRWSEFLEEPRLAARVAGARTRGGYLKDIKGFDSEFFAVAKTEADN
IDPQQRMALELTWEALEHARIPASSLRGQAVGVYIGSSTNDYSFLAVSDPTVAHPYAITGTSSSIIANRVSYFYDFHGPSVTIDTACSSSLVAIHQGVQA
LRNGEADVVVAGGVNALITPMVTLGFDEIGAVLAPDGRIKSFSADADGYTRSEGGGMLVLKRVDDARRDGDAILAVIAGSAVNHDGRSNGLIAPNQDAQA
DVLRRAYKDAGIDPRTVDYIEAHGTGTILGDPIEAEALGRVVGRGRPADRPALLGAVKTNVGHLESAAGAASMAKVVLALQHDKLPPSINFAGPSPYIDF
DAMRLKMITTPTDWPRYGGYALAGVSSFGFGGANAHVVVREVLPRDVVEKEPEPEPEPKAAAEPAEAPTLAGHALRFDEFGNIITDSAVAEEPEPELPGV
TEEALRLKEAALEELAAQEVTAPLVPLAVSAFLTSRKKAAAAELADWMQSPEGQASSLESIGRSLSRRNHGRSRAVVLAHDHDEAIKGLRAVAAGKQAPN
VFSVDGPVTTGPVWVLAGFGAQHRKMGKSLYLRNEVFAAWIEKVDALVQDELGYSVLELILDDAQDYGIETTQVTIFAIQIALGELLRHHGAKPAAVIGQ
SLGEAASAYFAGGLSLRDATRAICSRSHLMGEGEAMLFGEYIRLMALVEYSADEIREVFSDFPDLEVCVYAAPTQTVIGGPPEQVDAILARAEAEGKFAR
KFATKGASHTSQMDPLLGELTAELQGIKPTSPTCGIFSTVHEGRYIKPGGEPIHDVEYWKKGLRHSVYFTHGIRNAVDSGHTTFLELAPNPVALMQVALT
TADAGLHDAQLIPTLARKQDEVSSMVSTMAQLYVYGHDLDIRTLFSRASGPQDYANIPPTRFKRKEHWLPAHFSGDGSTYMPGTHVALPDGRHVWEYAPR
DGNVDLAALVRAAAAHVLPDAQLTAAEQRAVPGDGARLVTTMTRHPGGASVQVHARIDESFTLVYDALVSRAGSESVLPTAVGAATAIAVADGAPVAPET
PAEDADAETLSDSLTTRYMPSGMTRWSPDSGETIAERLGLIVGSAMGYEPEDLPWEVPLIELGLDSLMAVRIKNRVEYDFDLPPIQLTAVRDANLYNVEK
LIEYAVEHRDEVQQLHEHQKTQTAEEIARAQAELLHGKVGKTEPVDSEAGVALPSPQNGEQPNPTGPALNVDVPPRDAAERVTFATWAIVTGKSPGGIFN
ELPRLDDEAAAKIAQRLSERAEGPITAEDVLTSSNIEALADKVRTYLEAGQIDGFVRTLRARPEAGGKVPVFVFHPAGGSTVVYEPLLGRLPADTPMYGF
ERVEGSIEERAQQYVPKLIEMQGDGPYVLVGWSLGGVLAYACAIGLRRLGKDVRFVGLIDAVRAGEEIPQTKEEIRKRWDRYAAFAEKTFNVTIPAIPYE
QLEELDDEGQVRFVLDAVSQSGVQIPAGIIEHQRTSYLDNRAIDTAQIQPYDGHVTLYMADRYHDDAIMFEPRYAVRQPDGGWGEYVSDLEVVPIGGEHI
QAIDEPIIAKVGEHMSRALGQIEADRTSEVGKQ

(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)	1.91 (0.44)	1.28 (0.54)
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

Rv3800c/pks13, gene len: 5201 bp, num TA sites: 58

condition	dataset	call	medium	method	notes
in-vitro	DeJesus 2017 mBio	essential	7H9	HMM	fully saturated, 14 TnSeq libraries combined
in-vitro	Sassetti 2003 Mol Micro	essential	7H9	TRASH	essential if hybridization ratio<0.2
in-vivo (mice)	Sassetti 2003 PNAS	no data	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	essential	M9 minimal+cholesterol	Gumbel	3 replicates; Padj<0.05
differentially essential in cholesterol	Griffin 2011 PPath	NO (LFC=0.0)	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	essential	7H9	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
in-vivo (mice)	Smith 2022 eLife	essential	BL6 mice	HMM	6 replicates (raw data in Subramaniam 2017, PMID 31752678)
differentially essential in mice	Smith 2022 eLife	NO (LFC=0.0)	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	essential	YM rich medium	HMM	7H9 supplemented with ~20 metabolites (amino acids, vitamins)
differentially essential in YM rich medium	Minato 2019 mSys	NO (LFC=0.0)	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:
- Rv0023 (-)

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

Binds To:
- No bindings to other targets were found.
Bound By:
- Rv2009 (vapB15) (Direct binding)
- Rv0678 (-) (Upstream of operon)
- Rv1033c (trcR) (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:
- Rv0023 (-)

Property	Value	Creator	Evidence	PMID	Comment
Interaction	PhysicalInteraction Rv3801c	sourish10	TAS		Affinity purification (Physical interaction) SK. Parker, RM. Barkley et al. Mycobacterium tuberculosis Rv3802c encodes a phospholipase/thioesterase and is inhibited by the antimycobacterial agent tetrahydrolipstatin. PLoS ONE 2009
Interaction	ActivatedBy Rv2794c	shahanup86	IDA		Affinity purification (Physical interaction) C. Chalut, L. Botella et al. The nonredundant roles of two 4'-phosphopantetheinyl transferases in vital processes of Mycobacteria. Proc. Natl. Acad. Sci. U.S.A. 2006
Name	polyketide synthase 13	mjackson	IMP		Claisen-type condensation
Name	polyketide synthase 13	mjackson	IDA		Claisen-type condensation
Citation	Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. K. Takayama, C. Wang et al. Clin. Microbiol. Rev. 2005	jjmcfadden		15653820	Inferred from direct assay
Other	EC:	jjmcfadden			Inferred from direct assay K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005
Citation	Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. OA. Trivedi,P. Arora,V. Sridharan,R. Tickoo,D. Mohanty,RS. Gokhale Nature 2004	extern:JZUCKER		15042094	Inferred from experiment
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	extern:JZUCKER	NR		Inferred from experiment OA. Trivedi,P. Arora,V. Sridharan,R. Tickoo,D. Mohanty,RS. Gokhale Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature 2004
Citation	Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. K. Takayama, C. Wang et al. Clin. Microbiol. Rev. 2005	extern:JZUCKER		15653820	Traceable author statement
Term	EC:2.1.1.- Transferases. Transferring one-carbon groups. Methyltransferases. - NR	extern:JZUCKER	NR		Traceable author statement K. Takayama, C. Wang et al. Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin. Microbiol. Rev. 2005

TB Genome Annotation Portal