PKS18_MYCTU
ID PKS18_MYCTU Reviewed; 393 AA.
AC P9WPF1; L0T6G2; Q79FQ0; Q7D8I1;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Alpha-pyrone synthesis polyketide synthase-like Pks18;
DE EC=2.3.1.- {ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723, ECO:0000269|PubMed:15984864};
DE AltName: Full=Alpha-pyrone synthesis polyketide synthase type III Pks18;
DE AltName: Full=Chalcone synthase-like protein;
DE Short=CHS-like;
GN Name=pks18; OrderedLocusNames=Rv1372;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS A POLYKETIDE SYNTHASE, STARTER UNIT SPECIFICITY, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF ALA-148;
RP LYS-318 AND LEU-348.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=12941968; DOI=10.1074/jbc.m306714200;
RA Saxena P., Yadav G., Mohanty D., Gokhale R.S.;
RT "A new family of type III polyketide synthases in Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 278:44780-44790(2003).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15984864; DOI=10.1021/ja052991s;
RA Arora P., Vats A., Saxena P., Mohanty D., Gokhale R.S.;
RT "Promiscuous fatty acyl CoA ligases produce acyl-CoA and acyl-SNAC
RT precursors for polyketide biosynthesis.";
RL J. Am. Chem. Soc. 127:9388-9389(2005).
RN [4] {ECO:0007744|PDB:1TED, ECO:0007744|PDB:1TEE}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF MUTANT PHE-205 IN COMPLEX WITH
RP SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, STARTER UNIT SPECIFICITY, SUBUNIT,
RP ACTIVE SITE, AND MUTAGENESIS OF THR-144; CYS-175; CYS-205; ALA-209 AND
RP CYS-275.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15286723; DOI=10.1038/nsmb809;
RA Sankaranarayanan R., Saxena P., Marathe U.B., Gokhale R.S., Shanmugam V.M.,
RA Rukmini R.;
RT "A novel tunnel in mycobacterial type III polyketide synthase reveals the
RT structural basis for generating diverse metabolites.";
RL Nat. Struct. Mol. Biol. 11:894-900(2004).
CC -!- FUNCTION: Involved in the biosynthesis of tri- and tetraketide alpha-
CC pyrones. Pks18 catalyzes the extension of medium- and long-chain
CC aliphatic acyl-CoA substrates by using malonyl-CoA as an extender
CC molecule to synthesize polyketide products.
CC {ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723,
CC ECO:0000269|PubMed:15984864}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexanoyl-CoA + 2 malonyl-CoA = 4-hydroxy-6-
CC pentylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:43452,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:62620, ChEBI:CHEBI:66958;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43453;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 malonyl-CoA + octanoyl-CoA = 4-hydroxy-6-
CC heptylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:44284,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57386, ChEBI:CHEBI:84246;
CC Evidence={ECO:0000269|PubMed:15286723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44285;
CC Evidence={ECO:0000269|PubMed:15286723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-6-
CC undecylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:43460,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:57384, ChEBI:CHEBI:84149;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723,
CC ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43461;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723,
CC ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-6-(2-
CC oxotridecyl)pyran-2-one + 3 CO2 + 4 CoA; Xref=Rhea:RHEA:43368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57375, ChEBI:CHEBI:57384, ChEBI:CHEBI:84150;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723,
CC ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43369;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723,
CC ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexadecanoyl-CoA + 2 malonyl-CoA = 4-hydroxy-6-
CC pentadecylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:44260,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:57384, ChEBI:CHEBI:84168;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44261;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H(+) + hexadecanoyl-CoA + 3 malonyl-CoA = 4-hydroxy-6-(2-
CC oxoheptadecyl)pyran-2-one + 3 CO2 + 4 CoA; Xref=Rhea:RHEA:44268,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57379, ChEBI:CHEBI:57384, ChEBI:CHEBI:84171;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44269;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15286723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 malonyl-CoA + octadecanoyl-CoA = 4-hydroxy-6-
CC heptadecylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:44280,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57394, ChEBI:CHEBI:84169;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44281;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 H(+) + 3 malonyl-CoA + octadecanoyl-CoA = 4-hydroxy-6-(2-
CC oxononadecyl)pyran-2-one + 3 CO2 + 4 CoA; Xref=Rhea:RHEA:44272,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57394, ChEBI:CHEBI:84172;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44273;
CC Evidence={ECO:0000269|PubMed:12941968, ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-6-
CC nonadecylpyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:44264,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57380, ChEBI:CHEBI:57384, ChEBI:CHEBI:84170;
CC Evidence={ECO:0000269|PubMed:12941968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44265;
CC Evidence={ECO:0000269|PubMed:12941968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=eicosanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-6-(2-
CC oxohenicosyl)pyran-2-one + 3 CO2 + 4 CoA; Xref=Rhea:RHEA:44276,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57380, ChEBI:CHEBI:57384, ChEBI:CHEBI:84173;
CC Evidence={ECO:0000269|PubMed:12941968};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44277;
CC Evidence={ECO:0000269|PubMed:12941968};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-decenoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-6-(non-8-
CC en-1-yl)-pyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:45868,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:84214, ChEBI:CHEBI:85479;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45869;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=9-decenoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-6-(2-
CC oxoundec-10-en-1-yl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45924, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84214,
CC ChEBI:CHEBI:85494; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45925;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-hydroxytetradecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-
CC hydroxy-6-(2-hydroxytridecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45856, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84198,
CC ChEBI:CHEBI:85474; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45857;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-hydroxypentadecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-
CC hydroxy-6-(14-hydroxytetradecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45872, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84205,
CC ChEBI:CHEBI:85481; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45873;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=15-hydroxypentadecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-
CC hydroxy-6-(16-hydroxy-2-oxohexadecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45928, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84205,
CC ChEBI:CHEBI:85495; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45929;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16-hydroxyhexadecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-
CC hydroxy-6-(15-hydroxypentadecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45864, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84207,
CC ChEBI:CHEBI:85477; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45865;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=16-hydroxyhexadecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-
CC hydroxy-6-(17-hydroxy-2-oxoheptadecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45920, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84207,
CC ChEBI:CHEBI:85492; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45921;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxyoctadecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-
CC hydroxy-6-(11-hydroxyheptadecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45860, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84202,
CC ChEBI:CHEBI:85475; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45861;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-hydroxyoctadecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-
CC hydroxy-6-(13-hydroxy-2-oxononadecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45916, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84202,
CC ChEBI:CHEBI:85490; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45917;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylhexadecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 6-
CC (hexadecan-2-yl)-4-hydroxy-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45876, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84182,
CC ChEBI:CHEBI:85482; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45877;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-methylhexadecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-
CC 6-(3-methyl-2-oxoheptadecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45932, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84182,
CC ChEBI:CHEBI:85496; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45933;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylundecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-6-
CC (2-methyldecyl)-pyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:45880,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:84183, ChEBI:CHEBI:85483;
CC Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45881;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methylundecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-6-
CC (4-methyl-2-oxododecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45936, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84183,
CC ChEBI:CHEBI:85497; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45937;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyltridecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-hydroxy-
CC 6-(11-methyldodecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45888, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84195,
CC ChEBI:CHEBI:85485; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45889;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyltridecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-hydroxy-
CC 6-(13-methyl-2-oxotetradecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45944, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84195,
CC ChEBI:CHEBI:85499; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45945;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyloctadecanoyl-CoA + 2 H(+) + 2 malonyl-CoA = 4-
CC hydroxy-6-(11-methylheptadecyl)-pyran-2-one + 2 CO2 + 3 CoA;
CC Xref=Rhea:RHEA:45884, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84181,
CC ChEBI:CHEBI:85484; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45885;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=12-methyloctadecanoyl-CoA + 3 H(+) + 3 malonyl-CoA = 4-
CC hydroxy-6-(13-methyl-2-oxononadecyl)pyran-2-one + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:45940, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:84181,
CC ChEBI:CHEBI:85498; Evidence={ECO:0000269|PubMed:15984864};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45941;
CC Evidence={ECO:0000269|PubMed:15984864};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.2 uM for lauroyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC KM=5.4 uM for palmitoyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC KM=6.1 uM for arachidoyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC KM=19.2 uM for hexanoyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC KM=49.2 uM for acetyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC KM=58.4 uM for malonyl-CoA (at 30 degrees Celsius and at pH 7.5)
CC {ECO:0000269|PubMed:12941968};
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15286723}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. Chalcone/stilbene
CC synthases family. {ECO:0000305}.
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DR EMBL; AL123456; CCP44131.1; -; Genomic_DNA.
DR PIR; A70958; A70958.
DR RefSeq; WP_003407185.1; NZ_NVQJ01000050.1.
DR RefSeq; YP_177803.1; NC_000962.3.
DR PDB; 1TED; X-ray; 2.25 A; A/B/C/D=1-393.
DR PDB; 1TEE; X-ray; 2.90 A; A/B/C/D=1-393.
DR PDBsum; 1TED; -.
DR PDBsum; 1TEE; -.
DR AlphaFoldDB; P9WPF1; -.
DR SMR; P9WPF1; -.
DR STRING; 83332.Rv1372; -.
DR DrugBank; DB08231; Myristic acid.
DR SwissLipids; SLP:000001035; -.
DR PaxDb; P9WPF1; -.
DR DNASU; 886797; -.
DR GeneID; 886797; -.
DR KEGG; mtu:Rv1372; -.
DR TubercuList; Rv1372; -.
DR eggNOG; COG3424; Bacteria.
DR OMA; PIWGLGC; -.
DR PhylomeDB; P9WPF1; -.
DR SABIO-RK; P9WPF1; -.
DR UniPathway; UPA00094; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IBA:GO_Central.
DR GO; GO:0009715; P:chalcone biosynthetic process; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0030639; P:polyketide biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.40.47.10; -; 2.
DR InterPro; IPR012328; Chalcone/stilbene_synt_C.
DR InterPro; IPR001099; Chalcone/stilbene_synt_N.
DR InterPro; IPR011141; Polyketide_synthase_type-III.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR11877; PTHR11877; 1.
DR Pfam; PF02797; Chal_sti_synt_C; 1.
DR Pfam; PF00195; Chal_sti_synt_N; 1.
DR PIRSF; PIRSF000451; PKS_III; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acyltransferase; Fatty acid metabolism; Lipid metabolism;
KW Reference proteome; Transferase.
FT CHAIN 1..393
FT /note="Alpha-pyrone synthesis polyketide synthase-like
FT Pks18"
FT /id="PRO_0000407320"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 175
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:15286723"
FT BINDING 221
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:15286723"
FT SITE 205
FT /note="Important for broad specificity for aliphatic long-
FT chain acyl-CoA starter units"
FT SITE 209
FT /note="Important for broad specificity for aliphatic long-
FT chain acyl-CoA starter units"
FT MUTAGEN 144
FT /note="T->F: Completely abolishes the polyketide synthase
FT activity with lauroyl-CoA and palmitoyl-CoA."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 148
FT /note="A->F,M,T: Cannot be recovered in the soluble form."
FT /evidence="ECO:0000269|PubMed:12941968"
FT MUTAGEN 175
FT /note="C->A: Loss of polyketide synthase activity."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 205
FT /note="C->A: No significant change in polyketide synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 205
FT /note="C->F: Efficiently catalyzed the synthesis of the
FT triketide pyrone of the C6 starter unit and shows weak
FT polyketide synthase activity with the C12 starter
FT molecule."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 209
FT /note="A->F: Retained reasonable polyketide synthase
FT activity with lauroyl-CoA but cannot use palmitoyl-CoA."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 275
FT /note="C->A: No significant change in polyketide synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:15286723"
FT MUTAGEN 318
FT /note="K->A: Unable to synthesize any polyketide products."
FT /evidence="ECO:0000269|PubMed:12941968"
FT MUTAGEN 348
FT /note="L->S: Increase in the synthesis of the tetraketide
FT products."
FT /evidence="ECO:0000269|PubMed:12941968"
FT STRAND 32..41
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 49..57
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 68..74
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:1TEE"
FT HELIX 102..125
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 135..144
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 151..159
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 177..191
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 196..204
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 206..208
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 215..223
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 226..236
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 247..256
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 272..277
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 281..299
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 310..312
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 335..344
FT /evidence="ECO:0007829|PDB:1TED"
FT HELIX 350..361
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 364..378
FT /evidence="ECO:0007829|PDB:1TED"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:1TED"
FT STRAND 382..390
FT /evidence="ECO:0007829|PDB:1TED"
SQ SEQUENCE 393 AA; 42032 MW; 317D24C33B9CFD42 CRC64;
MNVSAESGAP RRAGQRHEVG LAQLPPAPPT TVAVIEGLAT GTPRRVVNQS DAADRVAELF
LDPGQRERIP RVYQKSRITT RRMAVDPLDA KFDVFRREPA TIRDRMHLFY EHAVPLAVDV
SKRALAGLPY RAAEIGLLVL ATSTGFIAPG VDVAIVKELG LSPSISRVVV NFMGCAAAMN
ALGTATNYVR AHPAMKALVV CIELCSVNAV FADDINDVVI HSLFGDGCAA LVIGASQVQE
KLEPGKVVVR SSFSQLLDNT EDGIVLGVNH NGITCELSEN LPGYIFSGVA PVVTEMLWDN
GLQISDIDLW AIHPGGPKII EQSVRSLGIS AELAAQSWDV LARFGNMLSV SLIFVLETMV
QQAESAKAIS TGVAFAFGPG VTVEGMLFDI IRR
