ID   PIKA5_STRVZ             Reviewed;         281 AA.
AC   Q9ZGI1;
DT   08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   03-AUG-2022, entry version 58.
DE   RecName: Full=Thioesterase PikA5 {ECO:0000303|PubMed:12368286};
DE            EC=3.1.2.- {ECO:0000305|PubMed:12368286};
DE   AltName: Full=Editing thioesterase {ECO:0000303|PubMed:12368286};
DE   AltName: Full=Thioesterase II {ECO:0000303|PubMed:12368286};
DE            Short=TEII {ECO:0000303|PubMed:12368286};
DE   AltName: Full=Type II thioesterase {ECO:0000303|PubMed:12368286};
GN   Name=pikAV {ECO:0000303|PubMed:9770448};
GN   ORFNames=BN2537_6641 {ECO:0000312|EMBL:CUM38838.1};
OS   Streptomyces venezuelae.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=54571;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND DISRUPTION
RP   PHENOTYPE.
RC   STRAIN=ATCC 15439 / DSM 41110 / IMRU3627 / M-2140;
RX   PubMed=9770448; DOI=10.1073/pnas.95.21.12111;
RA   Xue Y., Zhao L., Liu H.W., Sherman D.H.;
RT   "A gene cluster for macrolide antibiotic biosynthesis in Streptomyces
RT   venezuelae: architecture of metabolic diversity.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:12111-12116(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 15439 / DSM 41110 / IMRU3627 / M-2140;
RA   Babu N.S., Beckwith C.J., Beseler K.G., Brison A., Carone J.V.,
RA   Caskin T.P., Diamond M., Durham M.E., Foxe J.M., Go M., Henderson B.A.,
RA   Jones I.B., McGettigan J.A., Micheletti S.J., Nasrallah M.E., Ortiz D.,
RA   Piller C.R., Privatt S.R., Schneider S.L., Sharp S., Smith T.C.,
RA   Stanton J.D., Ullery H.E., Wilson R.J., Serrano M.G., Buck G., Lee V.,
RA   Wang Y., Carvalho R., Voegtly L., Shi R., Duckworth R., Johnson A.,
RA   Loviza R., Walstead R., Shah Z., Kiflezghi M., Wade K., Ball S.L.,
RA   Bradley K.W., Asai D.J., Bowman C.A., Russell D.A., Pope W.H.,
RA   Jacobs-Sera D., Hendrix R.W., Hatfull G.F.;
RL   Submitted (AUG-2015) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION.
RX   PubMed=10421766; DOI=10.1016/s1074-5521(99)80087-8;
RA   Tang L., Fu H., Betlach M.C., McDaniel R.;
RT   "Elucidating the mechanism of chain termination switching in the
RT   picromycin/methymycin polyketide synthase.";
RL   Chem. Biol. 6:553-558(1999).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX   PubMed=12368286; DOI=10.1074/jbc.m207770200;
RA   Kim B.S., Cropp T.A., Beck B.J., Sherman D.H., Reynolds K.A.;
RT   "Biochemical evidence for an editing role of thioesterase II in the
RT   biosynthesis of the polyketide pikromycin.";
RL   J. Biol. Chem. 277:48028-48034(2002).
CC   -!- FUNCTION: Involved in the biosynthesis of 12- and 14-membered ring
CC       macrolactone antibiotics such as methymycin, neomethymycin, narbomycin
CC       and pikromycin (PubMed:9770448, PubMed:10421766). Responsible for
CC       removing mis-formed acyl moieties (aberrant decarboxylation) that are
CC       bound to the PKS and could block it (PubMed:10421766, PubMed:12368286).
CC       Catalyzes the cleavage of methylmalonyl-[acp] (PubMed:12368286). It
CC       exhibits some acyl-group specificity, and catalyzes the cleavage of
CC       propionyl and butyryl derivatives faster than acetyl malonyl or
CC       methylmalonyl derivatives (PubMed:12368286).
CC       {ECO:0000269|PubMed:10421766, ECO:0000269|PubMed:12368286,
CC       ECO:0000269|PubMed:9770448}.
CC   -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:9770448}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene produce less than 5% of
CC       methymycin, neomethymycin and pikromycin. {ECO:0000269|PubMed:9770448}.
CC   -!- SIMILARITY: Belongs to the thioesterase family. {ECO:0000305}.
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DR   EMBL; AF079138; AAC69333.1; -; Genomic_DNA.
DR   EMBL; LN881739; CUM38838.1; -; Genomic_DNA.
DR   PIR; T17413; T17413.
DR   AlphaFoldDB; Q9ZGI1; -.
DR   SMR; Q9ZGI1; -.
DR   ESTHER; strve-PIKAV; Thioesterase.
DR   PATRIC; fig|54571.11.peg.3233; -.
DR   BioCyc; MetaCyc:MON-18410; -.
DR   BRENDA; 2.3.1.239; 6106.
DR   BRENDA; 2.3.1.240; 6106.
DR   BRENDA; 3.1.2.2; 6106.
DR   BRENDA; 3.1.2.20; 6106.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0033068; P:macrolide biosynthetic process; IDA:UniProtKB.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR020802; PKS_thioesterase.
DR   InterPro; IPR012223; TEII.
DR   InterPro; IPR001031; Thioesterase.
DR   PANTHER; PTHR11487; PTHR11487; 1.
DR   Pfam; PF00975; Thioesterase; 1.
DR   SMART; SM00824; PKS_TE; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Hydrolase.
FT   CHAIN           1..281
FT                   /note="Thioesterase PikA5"
FT                   /id="PRO_0000436361"
FT   REGION          26..249
FT                   /note="Thioesterase"
FT                   /evidence="ECO:0000305"
FT   ACT_SITE        99
FT                   /note="Nucleophile; for thioesterase activity"
FT                   /evidence="ECO:0000305"
FT   ACT_SITE        233
FT                   /note="Proton acceptor; for thioesterase activity"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   281 AA;  31700 MW;  2706923293678CD8 CRC64;
     MTDRPLNVDS GLWIRRFHPA PNSAVRLVCL PHAGGSASYF FRFSEELHPS VEALSVQYPG
     RQDRRAEPCL ESVEELAEHV VAATEPWWQE GRLAFFGHSL GASVAFETAR ILEQRHGVRP
     EGLYVSGRRA PSLAPDRLVH QLDDRAFLAE IRRLSGTDER FLQDDELLRL VLPALRSDYK
     AAETYLHRPS AKLTCPVMAL AGDRDPKAPL NEVAEWRRHT SGPFCLRAYS GGHFYLNDQW
     HEICNDISDH LLVTRGAPDA RVVQPPTSLI EGAAKRWQNP R