VERA_PENPO
ID VERA_PENPO Reviewed; 2566 AA.
AC A0A1V6NYI6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Highly reducing polyketide synthase verA {ECO:0000303|PubMed:34093475};
DE Short=HR-PKS verA {ECO:0000303|PubMed:34093475};
DE EC=2.3.1.- {ECO:0000305|PubMed:34093475};
DE AltName: Full=Cluster 4 protein A {ECO:0000303|PubMed:34093475};
DE AltName: Full=Verrucosidin biosynthesis cluster protein A {ECO:0000303|PubMed:34093475};
GN Name=verA {ECO:0000303|PubMed:34093475};
GN Synonyms=cl4A {ECO:0000303|PubMed:34093475}; ORFNames=PENPOL_c002G03804;
OS Penicillium polonicum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=60169;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IBT 4502;
RX PubMed=28368369; DOI=10.1038/nmicrobiol.2017.44;
RA Nielsen J.C., Grijseels S., Prigent S., Ji B., Dainat J., Nielsen K.F.,
RA Frisvad J.C., Workman M., Nielsen J.;
RT "Global analysis of biosynthetic gene clusters reveals vast potential of
RT secondary metabolite production in Penicillium species.";
RL Nat. Microbiol. 2:17044-17044(2017).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=34093475; DOI=10.3389/fmicb.2021.660871;
RA Valente S., Piombo E., Schroeckh V., Meloni G.R., Heinekamp T.,
RA Brakhage A.A., Spadaro D.;
RT "CRISPR-Cas9-Based Discovery of the Verrucosidin Biosynthesis Gene Cluster
RT in Penicillium polonicum.";
RL Front. Microbiol. 12:660871-660871(2021).
CC -!- FUNCTION: Highly reducing polyketide synthase (HR-PKS); part of the
CC gene cluster that mediates the biosynthesis of the neurotoxin
CC verrucosidin, a methylated alpha-pyrone polyketide that inhibits
CC oxidative phosphorylation in mitochondria and thereby causes
CC neurological diseases (PubMed:34093475). The carbon backbone of
CC verrucosidin is synthesized by the HR-PKS verA, and further modified by
CC the other verrucodidin cluster enzymes (Probable).
CC {ECO:0000269|PubMed:34093475, ECO:0000305|PubMed:34093475}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:34093475}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:34093475}.
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; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:34093475}.
CC -!- DISRUPTION PHENOTYPE: Does not affect the ability to grow nor
CC conidiation (PubMed:34093475). Abolishes the production of verrucosidin
CC (PubMed:34093475). Slightly reduced virulence 7 days after the
CC inoculation on apples cultivar Ambrosia (PubMed:34093475).
CC {ECO:0000269|PubMed:34093475}.
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DR EMBL; MDYM01000002; OQD69647.1; -; Genomic_DNA.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000191408; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 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; 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; IPR013217; Methyltransf_12.
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; 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; 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; PF08242; Methyltransf_12; 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; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2566
FT /note="Highly reducing polyketide synthase verA"
FT /id="PRO_0000455371"
FT DOMAIN 2411..2489
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 6..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 35..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 554..880
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 950..1246
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1386..1581
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 2127..2294
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2505..2540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2514..2533
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 176
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 648
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 982
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2449
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2566 AA; 279959 MW; 0665272EC9F2EB27 CRC64;
MTPEPIAIIG TGCKFPGSAS SPSRLWDLLR NPKTVASEPP STRFDNRSFY DPDPSHPGTT
NTKESYFLSE DIRLFDSAFF NISASEAEGI DPQQRLLLET VYESLEIAGQ RLEALQGSST
GIFCGVMGND WEHRVGFDDK AIPRYAATGL ARNNIANRVS YFFDWHGPSL VVDTACSSSL
VALHQAVTAL RQGECSVAVA AGTNLLLHPN IYISTSNLQM LSPNGRGRMW DAKADGYARG
EGIGALVLKC LSDAIADGDP IECVIRATGV NQDGRTMGLT MPSSKAQLAL IESTYAQAGL
DPKTRPEDRC QYFEAHGTGT LAGDPQEASA IYKSFFGDSS QHVSDNDPLY VGSIKTVVGH
TEGTAGIAGV IKASLSIQHG TIFPNLLFDE LNPELQRFTP RLKVPTETMP WPTLAPNIPR
RVSVNSFGFG GTNAHAILES YDIECDENWN GIPPQISNPI VLPFLFSAAS ARSLGTMLSN
YEEYLRSNPK IHLMDLAWTL MKRRSMLAYR VVLCAPTIEV LIIKIREELE LRKINNPSTI
TAQPPSGQKR ILGIFTGQGA QWPQMGLDLV THTSEGRQLF EEMHQSLLSL PIELQPTFSL
FDELAAAQPM SRLHEAVLSQ PLCAALQIIL VNFLTAVGIS FETVVGHSSG EIAAAYSAGI
LSASDCIRVA YLRGRVAGLA GAPNGQPGAM LAVGLSFATA NLLCLEPGLQ GRVHVAASNS
PSSVTLSGDQ DAIHEVEQRL QVEGKFARML RVDTAYHSHH MQPCAKPYLL DMDAAQVKLG
LQMNTRWYSS VHDAQEINLD EHGQSLTGEY WKNNMVSPVL FSAALLAALT SDGGPPDVIV
EIGPHPALKG PAQQTISDAL PSAGGSEIPY IGLSNRGASG IESLANAIGL LCAHLGPNSI
DLARYFSLFD HKYTPKVVRG LPAYPFDHRQ RHWFETRKLK NHLHNGGLLH PLLGSLEADT
ADGEWRWRHY LRREELEWLD GHQIQSRTVF PATGYIAMAL EAAGIFAAGQ SMRLVQIQRL
SIDQAITFSD ESSTGIETLF RLSGLQSQGD QVTGTFNCHA NIGGRLVNCA SGKLLICWGN
PETSMLPSQT PPAADAGAVD IKDFYQSLAK LGYNYTGAFQ GITSLARQKD MSTGQIINMG
QLSHESSLLF HPVMMDTSLQ MLLGALGAPG DGSLYTLMVP TGIERVTINP AFCGPKGAKA
AGRTLFADAF ITQLDTDGCS GAVEVFTQEG NGMVQMEGVH ISPLGPPDRQ RQPFSEIAWG
PLTPDAGLHS YPYPADLMNH TLLMEQISLI NIKQVVDQLT DKDRSGLDWH RSRVVAWMEH
VLAMTRTGKH PTCRSEWLDG TQEDIEVLLE RLAPSVTGLL AGVVGANMLR FLRGETSMLE
EARKDDVLSR FYKEDPESKT MNDRLGDLVG QIAFRYPRMK ILEIGAGSGS ATKSILERIG
SSYHSYTFTD ISPGFFEEAK QQFAEHQDHF IYQVLNVEKD PSKQGFEDDS YDLVIAANVL
HATKSMKDTM TNVRRLLKPG GYLGLMEVTN TSTIGISFCV GGFEGWWAGE GDGRVWGPML
NASNWENVLQ DTGFGGIDTI TTLGDARLSA YSVLVSQAVD DRMKVLRQPL SPAHQLKDTA
GELVIVGGEK DQTVSLVEEV AHLLEPFFAR IVPVQTLELL KGVNISPYAT VLSLVDMDGP
CFEYLSQSRL QGLQALTVAA RKMLWVTTGR ECDSPHLGMS KGWLKCLSYE HPEAQYQYLN
ITDDSTEEST LIAATLMRLV RTDEGNDYSL SSRTSATEPE LRFQNGTMSI PRLRASPELN
DRYVAGQQLV HKPVNLLEST VRMLPSAKGH YALHLEDKSL VSSHRADIDT ELVRIRTRYS
TIQAVRVGKD DVFLHLVLGE QEHSHRRLLA YSKDHASIIT TPMSWCCDLP DAVRPEFENS
FLQATLAAVL ARVLVQQATP GSVLWAHEAS GVLQQAIRIH AVASGVRPHF TTSSQSLPME
GVSFIHPLVT SRKLVGYLPQ DVSVAACFEV EEQGDEGIFS RIKSLLPQCV TVEDTHSLWR
TSQQLPEHGN VHHRHLGESL NVASAMAIQF VTSDPTQPVD VKGLSALPPT PRTPKADCIV
KWTGSQNEAL NVQVKTASQT LTLSSQKTYL LVGMTGDLGR SICHWLITKG ARHVVLTSRS
PKVDPHWIQE MSKLGANVVP MQLDVSNRES LLHVCDKIQK YHPRIGGVVN GALVLNDCAF
DEMPLETMQA TFAAKVDGSI LLDELFRGDL DFFILMGSLT GIVGNWNQSA YSAATGFQSN
LIHQRRARNI VGSIIQPGII TSVGYISRKG SGLAQHVSNT VGSLLLSERD LHEVFAEAIL
AGHPETSRNP EIVAGMPMAN PVTQPDIIWY RNPLCWDFVD YRIQSSSANH AGDGNTCSMK
ARLESAASMS EAAEIVAAGL ADKVRSKFNL ASDIALTQDT QLSDLGIDSL VAVDLRSWFV
RELSVEIPML QILSGSSLRA LTADSVSKLP PTLLPGILSR DQDFKDVSGL TSPPEVPSDA
SRSSVSSGMD EIVTPESPSF DQVYRIAGDE MELTKPHQRP IPTPQL
