STR11_STRTC
ID STR11_STRTC Reviewed; 727 AA.
AC A0A384XHA3;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Phenylalanine ammonia-lyase str11 {ECO:0000303|PubMed:30258052};
DE Short=PAL {ECO:0000303|PubMed:30258052};
DE EC=4.3.1.24 {ECO:0000305|PubMed:30258052};
DE AltName: Full=Strobilurin biosynthesis cluster protein r11 {ECO:0000303|PubMed:30258052};
GN Name=str11 {ECO:0000303|PubMed:30258052};
OS Strobilurus tenacellus.
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Physalacriaceae; Strobilurus.
OX NCBI_TaxID=41251;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RC STRAIN=CBS 621.79;
RX PubMed=30258052; DOI=10.1038/s41467-018-06202-4;
RA Nofiani R., de Mattos-Shipley K., Lebe K.E., Han L.C., Iqbal Z.,
RA Bailey A.M., Willis C.L., Simpson T.J., Cox R.J.;
RT "Strobilurin biosynthesis in Basidiomycete fungi.";
RL Nat. Commun. 9:3940-3940(2018).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=563391; DOI=10.7164/antibiotics.30.806;
RA Anke T., Oberwinkler F., Steglich W., Schramm G.;
RT "The strobilurins--new antifungal antibiotics from the basidiomycete
RT Strobilurus tenacellus.";
RL J. Antibiot. 30:806-810(1977).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=6271595; DOI=10.1016/0014-5793(81)81190-8;
RA Becker W.F., von Jagow G., Anke T., Steglich W.;
RT "Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors
RT of the bc1 segment of the respiratory chain with an E-beta-methoxyacrylate
RT system as common structural element.";
RL FEBS Lett. 132:329-333(1981).
RN [4]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=29711574;
RX DOI=10.1002/(sici)1521-3773(19990517)38:10<1328::aid-anie1328>3.0.co;2-1;
RA Sauter H., Steglich W., Anke T.;
RT "Strobilurins: evolution of a new class of active substances.";
RL Angew. Chem. Int. Ed. 38:1328-1349(1999).
RN [5]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=12146165; DOI=10.1002/ps.520;
RA Bartlett D.W., Clough J.M., Godwin J.R., Hall A.A., Hamer M.,
RA Parr-Dobrzanski B.;
RT "The strobilurin fungicides.";
RL Pest Manag. Sci. 58:649-662(2002).
CC -!- FUNCTION: Phenylalanine ammonia-lyase; part of the gene cluster that
CC mediates the biosynthesis of strobilurin A, an antifungal polyketide
CC that contains a key beta-methoxyacrylate toxophore that targets the
CC complex III of the mitochondrial electron transport chain
CC (PubMed:30258052). Strobilurin biosynthesis begins with construction of
CC benzoyl CoA by step-wise elimination of ammonia from phenylalanine by
CC the phenylalanine ammonia-lyase str11, oxygenation by str8 and retro-
CC Claisen reaction to form benzoic acid, which is activated to its CoA
CC thiolester benzoyl CoA by the dedicated CoA ligase str10
CC (PubMed:30258052). Benzoyl CoA forms the starter unit for the highly
CC reducing polyketide synthase stpks1 that produces the polyketide
CC prestrobilutin A (PubMed:30258052). The FAD-dependent oxygenase str9
CC then catalyzes the key oxidative rearrangement responsible for the
CC creation of the beta-methoxyacrylate toxophore (PubMed:30258052). Str9
CC performs epoxidation of the 2,3 olefin of prestrobilutin A, followed by
CC Meinwald rearrangement to furnish the aldehyde intermediate (Probable).
CC Rapid enolization of the aldehyde intermediate would give the beta-
CC methoxyacrylate skeleton and methylations catalyzed by str2 and str3
CC complete the synthesis and lead to the peroduction of strobilurin A
CC (Probable). The short-chain dehydrogenase stl2 and the dehydrogenase
CC str4 play a role in the shunt pathway leading to the production of
CC bolineol (PubMed:30258052). The cluster encodes no obvious halogenase
CC gene that could be involved in production of strobilurin B, nor any
CC obvious dimethylallyl-transferase that could be involved in the
CC production of strobilurin G (Probable). It is possible that unknown
CC proteins encoded in, or near, the cluster (such as str1 or stl1) may
CC form new classes of halogenases or dimethylally-transferases, or that
CC the responsible genes are located elsewhere on the genome (Probable).
CC Similarly, proteins encoded by str5/str6 hydrolases appear to have no
CC chemical role in the biosynthesis of strobilurin A (Probable). Finally,
CC no obvious self-resistance gene is found within the cluster (Probable).
CC {ECO:0000269|PubMed:30258052, ECO:0000305|PubMed:30258052}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-phenylalanine = (E)-cinnamate + NH4(+);
CC Xref=Rhea:RHEA:21384, ChEBI:CHEBI:15669, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:58095; EC=4.3.1.24;
CC Evidence={ECO:0000255|RuleBase:RU003955};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30258052}.
CC -!- PTM: Contains an active site 4-methylidene-imidazol-5-one (MIO), which
CC is formed autocatalytically by cyclization and dehydration of residues
CC Ala-Ser-Gly. {ECO:0000250|UniProtKB:Q68G84}.
CC -!- BIOTECHNOLOGY: The structure of strobilurin A was used for the
CC development of the major class of beta-methoxyacrylate agricultural
CC fungicides since its beta-methoxyacrylate toxophore targets the Qo site
CC of complex III of the mitochondrial electron transport chain and
CC prevents adenosine triphosphate synthesis (PubMed:563391,
CC PubMed:6271595). Compounds such as azoxystrobin (Syngenta) and Kresoxim
CC methyl (BASF) are among the most widely used fungicides worldwide
CC (PubMed:29711574, PubMed:12146165). This class of antifungals are used
CC as effective treatments against a broad range of destructive fungal
CC plant pathogens and make significant contributions to food security
CC (PubMed:29711574, PubMed:12146165). The strobilurin fungicides are
CC estimated to have been worth 3.4 billion dollars in 2015 and they make
CC up 25% of the fungicide market and 6.7% of the total crop protection
CC market (PubMed:30258052). {ECO:0000269|PubMed:563391,
CC ECO:0000269|PubMed:6271595, ECO:0000303|PubMed:12146165,
CC ECO:0000303|PubMed:29711574, ECO:0000303|PubMed:30258052}.
CC -!- SIMILARITY: Belongs to the PAL/histidase family. {ECO:0000305}.
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DR EMBL; KY070339; ATV82120.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A384XHA3; -.
DR SMR; A0A384XHA3; -.
DR GO; GO:0005737; C:cytoplasm; IEA:InterPro.
DR GO; GO:0045548; F:phenylalanine ammonia-lyase activity; IEA:UniProtKB-EC.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-KW.
DR CDD; cd00332; PAL-HAL; 1.
DR Gene3D; 1.10.274.20; -; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR InterPro; IPR001106; Aromatic_Lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR022313; Phe/His_NH3-lyase_AS.
DR InterPro; IPR005922; Phe_NH3-lyase.
DR InterPro; IPR023144; Phe_NH3-lyase_shielding_dom_sf.
DR PANTHER; PTHR10362; PTHR10362; 1.
DR Pfam; PF00221; Lyase_aromatic; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR01226; phe_am_lyase; 1.
DR PROSITE; PS00488; PAL_HISTIDASE; 1.
PE 1: Evidence at protein level;
KW Lyase; Phenylalanine catabolism.
FT CHAIN 1..727
FT /note="Phenylalanine ammonia-lyase str11"
FT /id="PRO_0000449346"
FT ACT_SITE 105
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 271
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 361
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 367
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 397
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT BINDING 499
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
FT MOD_RES 211
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10122"
FT CROSSLNK 210..212
FT /note="5-imidazolinone (Ala-Gly)"
FT /evidence="ECO:0000250|UniProtKB:Q68G84"
SQ SEQUENCE 727 AA; 78360 MW; D53B80A80CB9E6E8 CRC64;
MPITHEQPNG FHSKQLNGSG IAKAKAMPYP SDLLSHFVKQ HLELESYKNG QEIEIDGYSL
SISAVSAAAR YNAPVILRDS STIRDRLEKA RSVIVEKIEG SKSVYGVSTG FGGSADTRTS
NTLALGNALL QHQHSGVLPS TTNTLSVLPL LDPIASTSMP ESWVRGAILI RINSLIRGHS
GVRWELIAKM VELLQANITP LVPLRGSISA SGDLSPLSYV AGTLMGNPSI RVFDGPAAFG
ARQIVSSVKA LEEHNITPIS LLAKEHLGIL NGTAFSASVA SLVLSDVTHL AMLAQVCTAM
GTEVLLGERM NYAPFIHAVA RPHPGQTEAA RTIWDLLSGS KLAHGHEEEV TIDQDQGELR
QDRYPLRTAP QFLGPQIEDI LSALNTVTLE CNSTTDNPLI DGETGDIHHG GNFQAMSVSN
AMEKTRLSLH HIGKLLFAQC AELVHPDMNR GLPPSLAATD PSINYHGKGI DIGIAAYVSE
LGYLANPVST HIQSAELHNQ AVNSLALISA RATINSLEVL SLLTSSYLYM LCQAYDLRAL
QADFRQGLAE IVQEELRAHF SAHIESLDES PLFDKVISSM YKELNHTTTM DAVPRMVKVA
GASTSLLVDF FMANQTSDAM SVAALTALPK FRETVALRAA AKLVALREEY LLGARGPAPA
SAWLGRTRPI YEFIRVTLGI RMHGTENLGV FQQGLGVQDV TIGQNVSLIH EAIRDGKMRG
VVVGLFA
