SRDA_NEUCR
ID SRDA_NEUCR Reviewed; 2382 AA.
AC Q7SHI6;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2003, sequence version 1.
DT 25-MAY-2022, entry version 129.
DE RecName: Full=Highly reducing polyketide synthase srdA {ECO:0000303|PubMed:30908040};
DE Short=HRPKS sdrA {ECO:0000303|PubMed:30908040};
DE EC=2.3.1.- {ECO:0000305|PubMed:30908040};
DE AltName: Full=Polyketide synthase gene cluster 6 protein pks-6 {ECO:0000303|PubMed:28485098};
DE AltName: Full=Sordarial biosynthesis cluster protein srdA {ECO:0000303|PubMed:30908040};
GN Name=srdA {ECO:0000303|PubMed:30908040}; Synonyms=pks-6; ORFNames=NCU02918;
OS Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 /
OS FGSC 987).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Neurospora.
OX NCBI_TaxID=367110;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987;
RX PubMed=12712197; DOI=10.1038/nature01554;
RA Galagan J.E., Calvo S.E., Borkovich K.A., Selker E.U., Read N.D.,
RA Jaffe D.B., FitzHugh W., Ma L.-J., Smirnov S., Purcell S., Rehman B.,
RA Elkins T., Engels R., Wang S., Nielsen C.B., Butler J., Endrizzi M.,
RA Qui D., Ianakiev P., Bell-Pedersen D., Nelson M.A., Werner-Washburne M.,
RA Selitrennikoff C.P., Kinsey J.A., Braun E.L., Zelter A., Schulte U.,
RA Kothe G.O., Jedd G., Mewes H.-W., Staben C., Marcotte E., Greenberg D.,
RA Roy A., Foley K., Naylor J., Stange-Thomann N., Barrett R., Gnerre S.,
RA Kamal M., Kamvysselis M., Mauceli E.W., Bielke C., Rudd S., Frishman D.,
RA Krystofova S., Rasmussen C., Metzenberg R.L., Perkins D.D., Kroken S.,
RA Cogoni C., Macino G., Catcheside D.E.A., Li W., Pratt R.J., Osmani S.A.,
RA DeSouza C.P.C., Glass N.L., Orbach M.J., Berglund J.A., Voelker R.,
RA Yarden O., Plamann M., Seiler S., Dunlap J.C., Radford A., Aramayo R.,
RA Natvig D.O., Alex L.A., Mannhaupt G., Ebbole D.J., Freitag M., Paulsen I.,
RA Sachs M.S., Lander E.S., Nusbaum C., Birren B.W.;
RT "The genome sequence of the filamentous fungus Neurospora crassa.";
RL Nature 422:859-868(2003).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=19277664; DOI=10.1007/s00294-009-0236-z;
RA Nowrousian M.;
RT "A novel polyketide biosynthesis gene cluster is involved in fruiting body
RT morphogenesis in the filamentous fungi Sordaria macrospora and Neurospora
RT crassa.";
RL Curr. Genet. 55:185-198(2009).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=28485098; DOI=10.1111/1462-2920.13791;
RA Zhao Y., Ding J., Yuan W., Huang J., Huang W., Wang Y., Zheng W.;
RT "Production of a fungal furocoumarin by a polyketide synthase gene cluster
RT confers the chemo-resistance of Neurospora crassa to the predation by
RT fungivorous arthropods.";
RL Environ. Microbiol. 19:3920-3929(2017).
RN [4]
RP FUNCTION, AND PATHWAY.
RX PubMed=30908040; DOI=10.1021/acs.jnatprod.8b00983;
RA Zhao Z., Ying Y., Hung Y.S., Tang Y.;
RT "Genome mining reveals Neurospora crassa can produce the salicylaldehyde
RT sordarial.";
RL J. Nat. Prod. 82:1029-1033(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of sordarial, a salicylic aldehyde
CC structurally related to the phytotoxin pyriculol (PubMed:19277664,
CC PubMed:28485098, PubMed:30908040). The most interesting aspect of this
CC pathway is formation of an aromatic product from the highly reducing
CC polyketide synthase srdA (PubMed:30908040). SrdA synthesizes a reduced
CC polyketide chain from one molecule of acetyl-CoA and five molecules of
CC malonyl-CoA (PubMed:30908040). The polyketide chain is then reductively
CC released as an aldehyde (PubMed:30908040). The oxidoreductases srdC,
CC srdD and srdE then oxidize one of the hydroxy groups to facilitate the
CC intramolecular aldol condensation, followed by dehydration to yield a
CC salicylic aldehyde (PubMed:30908040). This aldehyde can undergo facile
CC reduction by endogenous reductases to yield the alcohol 1-hydroxy-2-
CC hydroxymethyl-3-pent-1,3-dienylbenzene (PubMed:30908040). The flavin-
CC dependent srdI counteract against the propensity of the aldehydes to be
CC reduced under physiological conditions and is responsible for
CC reoxidizing 1-hydroxy-2-hydroxymethyl-3-pent-1,3-dienylbenzene back to
CC the salicylic aldehyde (PubMed:30908040). This salicylic aldehyde is
CC then selectively epoxidized by the cupin-domain-containing
CC oxidoreductase srdB to yield the epoxide, which can be hydrolyzed
CC stereoselectively by the hydrolase srdG to give the final product
CC sordarial (PubMed:30908040). {ECO:0000269|PubMed:19277664,
CC ECO:0000269|PubMed:28485098, ECO:0000269|PubMed:30908040}.
CC -!- INDUCTION: Expression is up-reglated during sexual development
CC (PubMed:19277664). Expression is also up-reglated during confrontation
CC with the arthropod fungivore Drosophila melanogaster (PubMed:28485098).
CC {ECO:0000269|PubMed:19277664, ECO:0000269|PubMed:28485098}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; an enoyl reductase (ER)
CC domain that reduces enoyl groups to alkyl group; a ketoreductase (KR)
CC domain that catalyzes beta-ketoreduction steps; and an acyl-carrier
CC protein (ACP) that serves as the tether of the growing and completed
CC polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:30908040}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of the insecticidal
CC furocoumarin neurosporin A (PubMed:28485098). Does not affect the
CC fruiting body development and leads to normal fertility
CC (PubMed:19277664). {ECO:0000269|PubMed:19277664,
CC ECO:0000269|PubMed:28485098}.
CC -!- CAUTION: A recent genetics report associated srdA and its cluster with
CC the biosynthesis of furanocoumarin neurosporin A, a metabolite produced
CC by N.crassa for chemoresistance against predation by arthropod
CC fungivores (PubMed:28485098). However, based on the gene cluster
CC organization and predicted gene functions, this cluster is unlikely to
CC be involved in neurosporin A biosynthesis, but instead produces
CC compounds similar to pyriculol (PubMed:30908040).
CC {ECO:0000269|PubMed:28485098, ECO:0000269|PubMed:30908040}.
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DR EMBL; CM002236; EAA36364.1; -; Genomic_DNA.
DR RefSeq; XP_965600.1; XM_960507.1.
DR AlphaFoldDB; Q7SHI6; -.
DR SMR; Q7SHI6; -.
DR STRING; 5141.EFNCRP00000002314; -.
DR EnsemblFungi; EAA36364; EAA36364; NCU02918.
DR GeneID; 3881725; -.
DR KEGG; ncr:NCU02918; -.
DR VEuPathDB; FungiDB:NCU02918; -.
DR HOGENOM; CLU_000022_31_4_1; -.
DR InParanoid; Q7SHI6; -.
DR OMA; KDVQHYT; -.
DR Proteomes; UP000001805; Chromosome 1, Linkage Group I.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 3.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2382
FT /note="Highly reducing polyketide synthase srdA"
FT /id="PRO_0000449326"
FT DOMAIN 2298..2376
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..477
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 580..891
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 971..1274
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1668..1979
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2004..2180
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 672
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1003
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2335
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2382 AA; 256596 MW; FB4BF8278755E6C1 CRC64;
MAPHSTLDSD YSSGSSTPTS ASAAGDGFVD GLNGLNNGRA VDPQEPIAII GMGCRLPGGS
HSSSKLWELL KAGRTAQSRF PPSRFNIDGF YHPNSDRPGS LNMEGGYFIE DDIRGFENSF
FGINNLEATY MDPQQRKLLE VVFETFENAG FTLDQVSDAN IGCYVGNFVT DFITMQLKDS
EYTHRYSATG LGTTILANRI SHVFNMKGPS FVIDTACSSS LYCLHAAVAA LIAGECDSAI
VAGANLIQSP EQQLATMKAG VLSKTSTCHT FDSSADGYGR ADGIGAILVK RLSDAIRDGD
PIRSVIRGTA INSNGKTNGI TLPSADGQEA VIRKAYAQAG LGFNETDYIE CHGTGTAVGD
PIEVEAVSRV FKKPQGAPLL IGSVKSNLGH SEAASGLSSI IKVAMALEKG EIPPTYGVKN
INPKIKTDEW NVQIVTETTP WPKNLPHNAG RLFRRAGVNS FGYGGANAHA ILEAPQMHVP
VGYNRGSLPA SLTRSTLFLP FSGSNTAALE RRVTDIAAAI DFENVNIADL AYTLGVKRTH
LSTRGYILSG QDTLKDDLKP ENLRVALQGK TYSKLPLAFV FTGQGAQWPE MGKELMKEFP
SFRRTIQRLD AALQMLPHAP TWTLQGAILE PAKTSMINHA SRSQPVCTAV QIALVQLLAS
WGIKPESVIG HSSGEIAAAY TAGYLTPEQS IIIAYYRGHC VTKSTMVGAM MAAGLGAEDA
NKKISELDLV GKIRVACVNS PESVTISGDT EGIETLRAQF DQAGTFARVL KTDGKAYHSH
HMAVIGQEYE DLLTEALDGD DFPTTSNGVR FISSVTDAVV NHAVGPAYWR ANLESPVLFA
NVVERLIKDT ASHLVELGPH SALELPIKQT RTKLNISETK VHYGSALSRG KNSITTILNL
VGDLFLHGHD ISFKGVNYVD SAFNSPKARK NVKTQEKMLL DLPNYTWDYS GTVFNESRVS
VEWRNRKYPR HDLLGSQVHG GNGISTNWRN VVKAKDIPWM EGHKLDTTTV FPAAGYLAMA
VEAMCQVADV TKEQEPALSL RNVNITKALT LGSEETDAGV ELFTTLYPAQ LPGGATDAGW
YQFNISSYTN GTATTHANGL VKIDSAPAPL EVNLPIVPST MEPQAPRTWY GKFAKGGLNF
QGQFQSLTEI QNPRKKENPH TLAKTELRQG GGSGPSTESE YLIHPITIDA LFQAGIIAST
SGVVRELRAK VPVHIEEMHL RAPVGGQKEL KVNATSEAVG FGTIRVDGEL FDDEGRVFLQ
INRCRQVSYQ SGIQQEAGDE RHPMLRVVWK PDVTRLGAGD AKEFSQYIEQ YAAKSESKVD
DATVRLGAAL DLLIHKHPRL RILNLDVNLT EFLVDTLRLE TDFKKCKTLV SGSYSEDGTL
TFEDLTNEGK TSTAAQVFDV VILGSKAQEL EAAKELVDEN GSIIVNGSPA DADKLQTLGF
TTLQAPSDTI LAQTPQEITA KQQKTLSKQV LIVERNADHV LNSAIAAQAK KITGLEAKRI
PLESVTADII AAHTRVISTI ELENPVLSRV TEDEMKHIKT LTDNCTNLVW VTGGRLFQSA
SPEHAVVYGL SRALMLEQPS LRFFVVDVDH EGTPVERSAK HVVEVLQQAL IEADPDYEFV
QNAGLLHVSR FVPEETLNRV FREKQGAEKL ALPLKDARPF RLGTDMVGQI DSIFFRREEA
KDVQLADGHV EVSVKAVGLN TKDLQAINGD GDNTSGSFCT SQYTAVVANV GTGVENLAVG
DRVVVMTPGY FATTESVPAW ACQKLADNED FTTLSSVPLQ LSTAIYAVNN RAHVQAGESV
LVITGSDIAA DQAAIRVAQL AGAEVFAVGE STNLPSERVF TKGDKALVAK LLKATEGRGV
DVVLNFANDA APISSIGNVF ADCGRLVHVG KSSLAEAIAT DSTLFRKSVT VTTFDIANIL
SLKTVAGQKI RSQLLADSIA LYRQGQLNLA SSPKVFDVSE VRDAFRALAA KGHSGSVVVS
LENEASLVPT LPLKYDTVLS PEKSYLLVGC LGGLGRSMSK WMLARGARKF VFMGRSGTDR
APARRLVEDL ELAGAQVTVV RGDVINMEDV ELAVNGIDGP IGGVIQAAMG LDEALFTTMP
RDYWLTGLKP KIVGSWNLHN AIRGRDSELD FFLMTSSISG SVGTATESNY CSANYFLDVF
ARHRHSLGLP ATSIGLGMIS EVGYLHENPE IEAMLLRKGI QAINEDEMLQ IIDASLATPT
AVPGSYDELA RAHVLTGLEP LGLKELRAKG FEGTSPVLGD PRASLLSAAL DESTDAASSN
AASGMPAEVA EAIATGASVE DAVLKMISKK FSNLVLIPED KLNLTKPISE VGVDSMLAAE
FRAWIFQAFK VDVPYLTLLS AAATLTLLSE LITKKMMEAQ DA
