SDNO_SORAA
ID SDNO_SORAA Reviewed; 3084 AA.
AC A0A1B4XBH3;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 1.
DT 03-AUG-2022, entry version 23.
DE RecName: Full=Highly reducing polyketide synthase sdnO {ECO:0000303|PubMed:27072286};
DE EC=2.3.1.- {ECO:0000305|PubMed:27072286};
DE AltName: Full=Sordarin/hypoxysordarin biosynthesis cluster protein O {ECO:0000303|PubMed:27072286};
GN Name=sdnO {ECO:0000303|PubMed:27072286};
OS Sordaria araneosa (Pleurage araneosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Sordariaceae; Sordaria.
OX NCBI_TaxID=573841;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, AND PATHWAY.
RC STRAIN=ATCC 36386 / NRRL 3196;
RX PubMed=27072286; DOI=10.1038/ja.2016.40;
RA Kudo F., Matsuura Y., Hayashi T., Fukushima M., Eguchi T.;
RT "Genome mining of the sordarin biosynthetic gene cluster from Sordaria
RT araneosa Cain ATCC 36386: characterization of cycloaraneosene synthase and
RT GDP-6-deoxyaltrose transferase.";
RL J. Antibiot. 69:541-548(2016).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of sordarin and hypoxysordarin,
CC glycoside antibiotics with a unique tetracyclic diterpene aglycone
CC structure (PubMed:27072286). First, the geranylgeranyl diphosphate
CC synthase sdnC constructs GGDP from farnesyl diphosphate and isopentenyl
CC diphosphate (PubMed:27072286). The diterpene cyclase sdnA then
CC catalyzes the cyclization of GGDP to afford cycloaraneosene
CC (PubMed:27072286). Cycloaraneosene is then hydroxylated four times by
CC the putative cytochrome P450 monooxygenases sdnB, sdnE, sdnF and sdnH
CC to give a hydroxylated cycloaraneosene derivative such as
CC cycloaraneosene-8,9,13,19-tetraol (PubMed:27072286). Although the order
CC of the hydroxylations is unclear, at least C8, C9 and C13 of the
CC cycloaraneosene skeleton are hydroxylated before the sordaricin
CC formation (PubMed:27072286). Dehydration of the 13-hydroxy group of the
CC hydroxylated cycloaraneosene derivative might be catalyzed by an
CC unassigned hypothetical protein such as sdnG and sdnP to construct the
CC cyclopentadiene moiety (PubMed:27072286). The FAD-dependent
CC oxidoreductase sdnN is proposed to catalyze the oxidation at C9 of the
CC hydroxylated cycloaraneosene derivative and also catalyze the Baeyer-
CC Villiger oxidation to give the lactone intermediate (PubMed:27072286).
CC The presumed lactone intermediate would be hydrolyzed to give an
CC acrolein moiety and a carboxylate moiety (PubMed:27072286). Then,
CC [4+2]cycloaddition would occur between the acrolein moiety and the
CC cyclopentadiene moiety to give sordaricin (PubMed:27072286). SdnN might
CC also be involved in the [4+2]cycloaddition after the hypothesized
CC oxidation to accommodate the oxidized product and prompt the
CC [4+2]cycloaddition (PubMed:27072286). GDP-6-deoxy-D-altrose may be
CC biosynthesized from GDP-D-mannose by the putative GDP-mannose-4,6-
CC dehydratase sdnI and the short-chain dehydrogenase sdnK
CC (PubMed:27072286). The glycosyltransferase sdnJ catalyzes the
CC attachment of 6-deoxy-D-altrose onto the 19-hydroxy group of sordaricin
CC to give 4'-O-demethylsordarin (PubMed:27072286). The methyltransferase
CC sdnD would complete the biosynthesis of sordarin (PubMed:27072286).
CC Sordarin can be further modified into hypoxysordarin (PubMed:27072286).
CC The unique acyl chain at the 3'-hydroxy group of hypoxysordarin would
CC be constructed by an iterative type I PKS sdnO and the trans-acting
CC polyketide methyltransferase sdnL. SdnL would be responsible for the
CC introduction of an alpha-methyl group of the polyketide chain
CC (PubMed:27072286). Alternatively, the putative beta-lactamase-like sdnR
CC might be responsible for the cleavage and transfer of the polyketide
CC chain from the PKS sdnO to sordarin (PubMed:27072286). Two putative
CC cytochrome P450 monooxygenases, sdnQ and sdnT, might catalyze the
CC epoxidations of the polyketide chain to complete the biosynthesis of
CC hypoxysordarin (PubMed:27072286). Transcriptional regulators sdnM and
CC sdnS are presumably encoded for the transcriptional regulation of the
CC expression of the sdn gene cluster (PubMed:27072286).
CC {ECO:0000269|PubMed:27072286}.
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000305|PubMed:27072286}.
CC -!- DOMAIN: SdnO consists of a ketosynthase domain, acyltransferase domain,
CC dehydratase domain, unassigned region, enoylreductase domain, beta-
CC ketoreductase domain, acyl carrier protein (ACP) and a
CC choline/carnitine acyltransferase domain (PubMed:27072286). The
CC polyketide chain might be transferred to the 3'-hydroxy group of
CC sordarin by the putative choline/carnitine acyltransferase domain of
CC SdnO because there is no obvious acyltransferase of the polyketide
CC chain in the sdn cluster (PubMed:27072286).
CC {ECO:0000305|PubMed:27072286}.
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DR EMBL; LC079035; BAV32159.1; -; Genomic_DNA.
DR SMR; A0A1B4XBH3; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.30.559.70; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 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; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR039551; Cho/carn_acyl_trans.
DR InterPro; IPR042231; Cho/carn_acyl_trans_2.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00755; Carn_acyltransf; 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 SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..3084
FT /note="Highly reducing polyketide synthase sdnO"
FT /id="PRO_0000441065"
FT DOMAIN 2363..2440
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 7..433
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 541..841
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27072286"
FT REGION 931..1243
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27072286"
FT REGION 1733..2045
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27072286"
FT REGION 2069..2252
FT /note="Catalytic ketoreductase (KRc) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27072286"
FT REGION 2445..2501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2864..3084
FT /note="Choline/carnitine acyltransferase domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27072286"
FT COMPBIAS 2447..2501
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000250|UniProtKB:L7X8J4"
FT ACT_SITE 632
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000250|UniProtKB:L7X8J4"
FT ACT_SITE 963
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000250|UniProtKB:L7X8J4"
FT MOD_RES 2400
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3084 AA; 332855 MW; 58126617F0154E48 CRC64;
MASPIPLAVV GIACRFPGDA TNPEKLWDLL AEGKSAWSRV PSDRWNEEAF LHPSPDDMNG
SHNHLGGHFL RQDVGEFDAG FFNVLPGEAA AMDPQQRLLL ETTYEAIESA GIPKESLAGS
KTAVYMAMFT RDYDRNVYKD MMSIPKYHVT GTGDAILANR ISYLFDLRGP SMTIDTGCSG
GMAAVAHACQ ALRSGVSDVA LAGAANLILS PDHMVGMSNL HMLNAEGKSY AFDDRGAGYG
RGEGIATLVI KRLDDAIKAN DPIRAIIRDA AVNQDGHTAG ITLPSGQAQE ALERQVWSNI
GLDPREVGYV EAHGTGTQAG DSAELEGISR VFCRGRTDSE SLTVGSIKSN IGHTECVSGL
AALIKSILVL EKGAIPPNVN YQTAKPGLDL DKRKLRVPTT LQKWSQPGVP RVSVNSFGYG
GTNAHAVLEK APETQRDSAS DSQEDVPRLF TLSAASQSSL QDMAASIAGW VSQERDSQPL
PTSRLQDIAY TLSERRSLMA WRFWSVASNE HELVDSLYEA SRSTENISKI SSSEPPPKIS
FIFTGQGAQW PGMGRELLQS NAVFAESISR SNKILAGLGA AWGLVDEILR DKGPSRLREA
ELAQPATTAI QIALVDLARH WGIVPDSVVG HSSGEIAAAY AAGYLSPQQA ITAAYYRGFS
SAVARSKGLG KGGMLAVGLG EDEVAPYLAR ISPENGEAVV ACQNSPKSVT ISGDDAAIAE
LSELLTKDDV FNRRLLVDTA YHSHHMEAAA DEYRSSLGDM EPRNSTGTIN MFSSVTGSLK
TDDKFDANYW VSNLVGKVRF RDALQALCQH DQTSSSPQTH RVFIEIGPHA ALAGPLRQSV
ADMPTPLPHS YTSALVRGTS ASQSALSMAG SLFSRGYPLN ISALNSASSL SSSSSPSVIP
NLPTYAWDHT KRHWHESRLS RDYRMRKHAY HDLLGLRMTD TTPLRPAWRH MVGVEGLPWL
RDHVVDGLIV FPGAGYMCMA LQAAEQLALD LPSHSKVKRM RLQNVAFLKG LVIPDSTRER
VEVQLVLTPL TGDNGPDNKL GYSFLVTAYT ADDDKWTEHC RGSVLIDLVS SSAASSQSTV
GFESQHQITY AEAVSSLNLQ PGEDIPPSEL YQTLRKGGNA YGPTFSGIQV FRLLPDNASE
DTSSANVALS TIAIPDIQSI MPAKHMQPHI IHPSTLDVLL HTTLPLVSRR LGVVGSVMPV
RIDDLVIDLG EQQLETKTDA QLRAITTLTG SGFRSAEADM LVFPAPSSEV DQGQLMPVIS
VMGMELRSLA ALDGAAAGDP ATENLSVEES RDICYEMKWV VDESFLSAEH LVNAVQQRDS
SFDTPLERCL GALDKYLGIK ALKEFMADLK VLEIAAAGDS NGECTLAFLD ALQTRGALPA
EYDLTAQPHG DALWQDKYPG VVTVRPLLDS MNHGLDGHYD IVFAAGSLNG SDGVTVQTSL
SNIRSLMKPG AVLVAIHDTN SSLSADVFSQ TGFNTQLSIP FDELSLTIAR AVGSASTTTP
VKLQFIAEPG FSTSTSIRTI IDNLPSTLTA KGVQIITAPE PCILNWTKGN LYDQDSDSEP
VTLNIVLDNG ASPILPTVTN GTPTFSNIVS LLQKQHSKVL WVSLSDDEQH KLNPQKHLIT
GVARTAHAEN ELLELVTVDV QQPISESTTS GLVNFLGDIA ASFPGLDGAA GETGTKKERE
YIYIGENHIL VPRVMSSPSL NRQIKKSKET VTSTENFVMT PLKLDIAGKD GPGTAHAATF
VEDESHRQPL GEDCVEIQAK AFGVGSSSWA SKGRPSSASS IAEYAGVITA IGSGVLISSG
LKIGDRVVAW AETSLSFASR PRIPASQVRV LPDHVSLSTG AGLPVSLMTA CHALREISNV
QPGQVVFIDG AASDIGQAAL LVARYLGAKV IVAVSTSDEA SFLQDKFGLP LANILPRASP
FLRHQLRKLL ASGGAIDAIL SCAGSAVPGE IIKTQKPFGT LVQVGGTTGA MTASAVNSTV
VSLDLGSFLT QTHPSKATRL FDMAMETVHR GLDLEPIRIA YLPMTNLNEA LKSARRHENM
TKYVVEVGQE AMVKVARPSY ILPKLDEHAT YVVAGGLGDL GQRFLRLMAK AGARYLVTLS
RSGAREGQQS ALERELNSLS PLSSLNLLCL KCDVSKEAKI QNSLAEIKAA GFPSVRGVIQ
ASLVLGDSTL DNMTAQDFDR VLQAKAFGTL HLQRVFVPEG LAFFISLSSA VNMIGSAGQA
NYNAANSLQD ALAQFDKSSD CFYMALNIGL IEDATVNSDV IIQSVQRQGL TTIYHDELDA
YFEYSLSAEA RQAGCHQAVI GFTPESIAKT SIVNGTAKTL MFTHVRRQIS KQGQTEDDDA
GGASGAVKTF AEFVAQGTHE QDDIEAFAAR AIANKLADLM LIEPEDVELD ESLNDFGLDS
LIAIELRNWI MRELGSPIQT SEVLGSENIW ALARKVTLRS VHVTGGAGGD ASSTGNSESM
ARTPSDSSTV PTSIPATPSR SPSREPPAKE TLTKSQQHLP IPDLTETLNM LVESRTAIGS
LEEKAEIERV IQDFLTTDGP ELVEILRSNN DSSSDARLDF YNNHLHLERR EPLQDHALFF
IGHLAEGEAG AAPPPKHTQA ERAAIITGAA MHFKQRLESG SLEQHKLNDI VLCMDTLQWL
FHTIQEPGVA TDLAQKYPSN NKVVAMRKGH IFEIDVHPED DYAALHQIFS DIIASSDSSS
DSIPKVSVLT TKPRHEWAVL RSQIQSLSPT NAETIDAIES CAFIVSLDHS SPETTSERST
SILLNDLHLS NRWLDKMLTF TVASNGVSSL LGENTMLDGL SARQLSEYMT NEIFTNPKLS
PPTSPPASTI RPLLFTLTPH VVETISQQIQ HNLSTYHPIS SSRHFYSQLN RAFLGSRGMR
SKGTVLVAIA MATRLFFGHY EPLWETVTLA KYKQGRIDWL QTLTPDMVAF VDSLIAIHSH
SLTSSSEVDW KGMNKLLKEV SISHVQNLQR VADGRGYVEA LYSLMGTAIS QGHDLPELFK
SEAWKQTDRH LSPKRAKTDC LGSGGYLRMQ EGGFLMPNPG SLFIHYEVHH RDPLVNVSGR
EEDVARFEGI LGACLGVVRR VVEG
