STR4_STRTC
ID STR4_STRTC Reviewed; 615 AA.
AC A0A3B1EFP9;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Dehydrogenase str4 {ECO:0000303|PubMed:30258052};
DE EC=1.1.-.- {ECO:0000305|PubMed:30258052};
DE AltName: Full=Strobilurin A biosynthesis cluster protein r4 {ECO:0000303|PubMed:30258052};
GN Name=str4 {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], INDUCTION, FUNCTION, 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: Dehydrogenase; part of the gene cluster that mediates the
CC biosynthesis of strobilurin A, an antifungal polyketide that contains a
CC key beta-methoxyacrylate toxophore that targets the complex III of the
CC mitochondrial electron transport chain (PubMed:30258052). Strobilurin
CC biosynthesis begins with construction of benzoyl CoA by step-wise
CC elimination of ammonia from phenylalanine by the phenylalanine ammonia-
CC lyase str11, oxygenation by str8 and retro-Claisen reaction to form
CC benzoic acid, which is activated to its CoA thiolester benzoyl CoA by
CC the dedicated CoA ligase str10 (PubMed:30258052). Benzoyl CoA forms the
CC starter unit for the highly reducing polyketide synthase stpks1 that
CC produces the polyketide prestrobilutin A (PubMed:30258052). The FAD-
CC dependent oxygenase str9 then catalyzes the key oxidative rearrangement
CC responsible for the creation of the beta-methoxyacrylate toxophore
CC (PubMed:30258052). Str9 performs epoxidation of the 2,3 olefin of
CC prestrobilutin A, followed by Meinwald rearrangement to furnish the
CC aldehyde intermediate (Probable). Rapid enolization of the aldehyde
CC intermediate would give the beta-methoxyacrylate skeleton and
CC methylations catalyzed by str2 and str3 complete the synthesis and lead
CC to the peroduction of strobilurin A (Probable). The short-chain
CC dehydrogenase stl2 and the dehydrogenase str4 play a role in the shunt
CC pathway leading to the production of bolineol (PubMed:30258052). The
CC cluster encodes no obvious halogenase gene that could be involved in
CC production of strobilurin B, nor any obvious dimethylallyl-transferase
CC that could be involved in the production of strobilurin G (Probable).
CC It is possible that unknown proteins encoded in, or near, the cluster
CC (such as str1 or stl1) may form new classes of halogenases or
CC dimethylally-transferases, or that the responsible genes are located
CC elsewhere on the genome (Probable). Similarly, proteins encoded by
CC str5/str6 hydrolases appear to have no chemical role in the
CC biosynthesis of strobilurin A (Probable). Finally, no obvious self-
CC resistance gene is found within the cluster (Probable).
CC {ECO:0000269|PubMed:30258052, ECO:0000305|PubMed:30258052}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:E4QP00};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30258052}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q12062}.
CC -!- INDUCTION: Induced in strobilurin-producing conditions (on CGC medium
CC after 6 days of growth). {ECO:0000269|PubMed:30258052}.
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 GMC oxidoreductase family. {ECO:0000305}.
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DR EMBL; KY070339; ATV82114.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3B1EFP9; -.
DR SMR; A0A3B1EFP9; -.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IEA:InterPro.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IEA:InterPro.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR012132; GMC_OxRdtase.
DR InterPro; IPR000172; GMC_OxRdtase_N.
DR InterPro; IPR007867; GMC_OxRtase_C.
DR PANTHER; PTHR11552; PTHR11552; 1.
DR Pfam; PF05199; GMC_oxred_C; 1.
DR Pfam; PF00732; GMC_oxred_N; 1.
DR PIRSF; PIRSF000137; Alcohol_oxidase; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Oxidoreductase.
FT CHAIN 1..615
FT /note="Dehydrogenase str4"
FT /id="PRO_0000449341"
FT ACT_SITE 552
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 45..46
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 66..67
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 123..126
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 585
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
FT BINDING 596..597
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:E4QP00"
SQ SEQUENCE 615 AA; 66352 MW; 96EA5B9BADE91CB1 CRC64;
MGASHSTVSD PHRFAVAITG SDDDVRSLQA HPTKSYDYIV VGGGTAGCVL ASRLSEDSRV
NVLLVEAGYS NHGVTNSIIP LAFPMLMKSK YDWNYETVGM AGINGRTSYW PRGRLLGGTS
SINGSMYHRC APEDFSAWVE EGAKGWEYEN MKPYFRKAEG YNPHPDHPNI DPALHGTVGP
AKVTHGPIAF LSQPITKDIL QSSINVGIRQ VHDFNTDVGP TGVGLFARNV FPNGTRVSAA
TGYLTPSVLA RPNLTVAVEC MAEKIVLSSD EKVPRAKGLI FSTSRDGQRF YVPASKELIL
SSGVIGTPQV LMLSGIGPAA ELAKHNIPVV RDLPVGEYLQ DHFSPGPMLI RAKKGTWDFI
LRPLGGLLAM VKWFFFGKGP LSSLSVQVAC FVRSDDKTFA HPQLPMHDGA KKYQVKDCCS
GPTAPDIELF FAPFLAPPLG MKYWPFPGLT SGMLLLKPAS YGTVKLASRN AWDYPLIDPN
YLSHESDIAL SIMGMRLLAR IARTKPFADS LDLPEDSDDK TSVFWPTDCN PDTVSDDDLE
AWARLHGQST GHPTSSARMG GSPSTSVVDS KLKVHGVEGL RVCDASCFPT QVSGHPAAVV
VAVAERAADL IKGVA
