PSPA_PENSO
ID PSPA_PENSO Reviewed; 2528 AA.
AC P0DUK1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-JUN-2021, sequence version 1.
DT 03-AUG-2022, entry version 5.
DE RecName: Full=Highly reducing polyketide synthase pspA {ECO:0000303|PubMed:31086874};
DE Short=HR-PKS pspA {ECO:0000303|PubMed:31086874};
DE EC=2.3.1.- {ECO:0000269|PubMed:31086874};
DE AltName: Full=Soppiline biosynthesis cluster protein A {ECO:0000303|PubMed:31086874};
GN Name=pspA {ECO:0000303|PubMed:31086874};
OS Penicillium soppii.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69789;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, AND PATHWAY.
RX PubMed=31086874; DOI=10.1039/c9ob00807a;
RA Kaneko A., Morishita Y., Tsukada K., Taniguchi T., Asai T.;
RT "Post-genomic approach based discovery of alkylresorcinols from a cricket-
RT associated fungus, Penicillium soppi.";
RL Org. Biomol. Chem. 17:5239-5243(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the alkylresorcinols called
CC soppilines (PubMed:31086874). The biosynthesis starts with the HR-PKS
CC pspA-catalyzed carbon chain assembly through nine chain elongation
CC cycles, using acetyl CoA and malonyl CoA as a starter and extender
CC units, respectively, to produce the polyketide soppiline A
CC (PubMed:31086874). In the first round, the KR, DH, and CMeT domains
CC work to produce 2-methyl-2-butenyl thioester (PubMed:31086874). In
CC rounds 2 to 5, the KR, DH, and ER domains fully catalyze the reduction
CC of the elongated beta-ketothioester, resulting in the insertion of
CC eight methylene units (PubMed:31086874). The unusual Z,E,Z-triene motif
CC is likely constructed during rounds 6 to 8 (PubMed:31086874).
CC Typically, the DH domain introduces a double bond at an alpha,beta-
CC position of an elongated polyketide chain, with the dehydration of a
CC beta-hydroxy group (PubMed:31086874). The last extension cycle would be
CC carried out with L-oriented beta-ketoreduction by the KR domain to
CC produce beta-hydroxy carboxylic acid soppiline A (PubMed:31086874). The
CC type III PKS pspB intercepts the elongated polyketide chain at round 8
CC from the HR-PKS pspA, followed by a tri-keto extension and
CC decarboxylative aldol cyclization to produce 1,3,5-trisubstituted
CC alkylresorcinol soppiline B (PubMed:31086874). Subsequently, the
CC cytochrome P450 monooxygenase pspC catalyzes three-step oxidations at
CC the C-4 methyl group to carboxylic acid to yield soppiline C
CC (PubMed:31086874). {ECO:0000269|PubMed:31086874}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 20 H(+) + 9 malonyl-CoA + 13 NADPH + S-adenosyl-
CC L-methionine = 9 CO2 + 10 CoA + 7 H2O + 13 NADP(+) + S-adenosyl-L-
CC homocysteine + soppiline A; Xref=Rhea:RHEA:66908, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:58349, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:167558; Evidence={ECO:0000269|PubMed:31086874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66909;
CC Evidence={ECO:0000269|PubMed:31086874};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31086874}.
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; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; 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:31086874}.
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DR AlphaFoldDB; P0DUK1; -.
DR SMR; P0DUK1; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0071704; P:organic substance metabolic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
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; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
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; 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; 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; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_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; 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; 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; SSF53335; SSF53335; 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 Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2528
FT /note="Highly reducing polyketide synthase pspA"
FT /id="PRO_0000452731"
FT DOMAIN 2447..2525
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..486
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 590..909
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 961..1230
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1409..1587
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1803..2119
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2143..2322
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 20..44
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 235
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2485
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2528 AA; 278974 MW; 4385B22DD2D569A8 CRC64;
MLAQDVEFVD LPPPEATAGA ATTDNETSSF NSNPVPTPSE ASSIGPPHQL PVPVPDGDQP
PLVEPMAICG MAMRLPGGIR DAEGFWDLLY NKRSGRCRVP KDRYNVENWF GPGKIGHVAS
EYGYFLDDVD LRNADASFWS MTKQEIEAMD PQQRLSLEVT YECLQNAGQR PEELRGRKIG
VYLGTFEGDW LELDGRDPQH YHMYRLTGYG DYMSANRIHY EFGFMGPSVT IRTACSSSLT
GLYDACHAIS AGDCDSAIVA CANIIYSPRT SITMQEQGVI SPSGFCKTFD ANADGYARGE
AVSAVYVKKL SDAIRDGDPI RSVIRSTCIN AGGKASTLTA PNTAAHETLI RRGHELAGVT
DFSKTAMIEC HGTGTAVGDP IETAAVANVF GEHGIYIGSV KTNLGHSEGA SGLASIIKMT
LALEHKIIPP NINFTTPNPK IPFERCKLKV PTEPLPWPKD RAELVGVNSF GIGGSNAHVL
LGSAASFGIG SVQQKIIASE QSAEVAMTEL TPRLLLFSAK HQQSLERMVA NHQAYFLSHP
ESLDDMAYSL ALKREELSHR SFCVTNGEDD WVPSRTHRTS GRAPPMLIFT FTGQGAQWAQ
MGKALIDQVP RFRRSIEKLD QVLQALPTPP RWKLIDEIRA SKKKSRLSEA ELSQPCCTAI
QIALVDILEH YGIHPDAVIG HSSGEIGAAY ASHAISGADA IQIAFYRGLV MCSLNPAERP
GGMAAVGLGA EELTPYLRPG VRVGCENSPN STTLTGDKVS LEETMKAIKE ANPDVFVRAL
QVDRAYHSHH METVAPEYVE LLTNQRVQAM DPSVKFFSSV TGRQVDQSKE LGPLYWAKNL
VSPVRFSTAM EELVQSLIGP KVFLEIGPHS ALAGPIRQIL QHHKSTDEYF NTLTRGSDSH
KDLLKAVGEM WLQNIPVNLT AVLGEGRFLP DLPLYPWHYE EPLWCESRLS KEWRLREFPH
HDILGSRVLE STDQNPSWRN ILRLDVVPWI KEHEVAGEIV FPGVGYICMA GEAIRQLTGE
TGFTARRVHI KAALVMHQGQ DVEVITQLQR IPLTNAADSK WYNFTVHSYN KGIWVKHIFG
QVCAGSDREH QAPSLESLPR QLSRRGWYRK MKEMGLEYGS RFMGLTDMTA HPIERKTIAT
VVNDIREGES KYAVHPVSLD CLLQAIVPAT FNGLTRRFQH LGIPTYMEEI YVCPPLQPEM
IIEACADEQP TAALSGSIIA VSNGHVTIDI RGLQMSAIGD AADASGQDPH AAVELEWRED
INLISDAAKL IHPAKDRTDL HHLLDRFASA SMMDTSTRLR GVEPTRSHLT HYQKWIESTA
DLIKLGKYPG LQPEDEIVEV SDAERVNIIE SLYLSLLETD AAATATAIYR IWKECQGIFT
GETDELELLL EGEVLHSLYD FMQNSEYRVF LELLAHRKPN LRVLEIGAGT GGTTATVLPA
LKSLYGERMY HSYTYTDISA GFFPQAKKRF ENYPGLEFAT LDISQDPLSQ GFEAESFDLI
IACNVLHATS TLQDTLTNVR RLLHPQGRLF LQELSPATKW INYVMGVLPG WWLGEQDGRY
PEPYIGIDQW DALLSQSGFS GINLVSHDGY LNNNIVARPA ADTQRQKRIT LLHSCEDSAS
VTTSISQLLS SAGFGIDLYA IENANIPTPT QQDIVSILDL DRPFFHDLHE SLFENLKGLL
SQLRDTDSGI LWVTRASQVG CKDPRYAMVN GVARVIRTEL NIDFATLELE DFEQETLALI
PQVLGEFQQR ISEPNINTTT EWAVVGQKPL ISRYHYIQVA EELKNNAVAD SSTVKKLEQS
RPGLVDTLCW KSMPISHALD ENDVLVQVKC VGMNFKDVLI STGVITEKSS IGRGLGYEGS
GLVLQVGSAV HKLSVGDRVI MSSSGSLTTT QQLDQRLCVK MPDSMTYEEG ATMSAVYCTA
IHCLLDVGGL RKGQSVLIHS ASGGVGIAAM YIAQMVGAEV YATVGSEEKT QSLMSTFNIP
RNRIFNSRTS EFLPRIMEET NGMGVDVVLN SLSGELLHAS WKCTAEFGTF VEIGRRDFVG
QGLLDMQPFE PNRSFVGFDL LLFSNKRPER IESIMTRAMD YYRAGFIQPI KPMTMFDAVS
IVDAIRYMQR GQHIGKIVIT MPENSTELSA EPPRQELALR QDRAYLFVGG LGGLGRSIAT
WLVEHGARHL VFLSRSAGNV PDDDPFVQEL AVLGCTTTRI SGDVSKLDDV LLAIRASGKP
VGGVLQSSMV LRDNSFVDMN WDEWLGAVQP KVLGTWNLHN ALLSEQPEEA LDFFFLFSSA
GAMSGQWGQA NYNAGNTFLD AFVAYRHSLG LPASTVNIGV IQDIGYVSQN PEILDSLRST
AQYLMREPEL LESIELMLHR SSPAESVVDH AVGRYVTRSQ IGIGMRSTVP MDAPSNRTIW
RKDPRMLVYR NLEVQSGPVS SSTGSDQVLT QFLREIGSNM TMLKAPETAE LLAGEIGRTL
FGFLMRADTE VVDLDAPLAS VGIDSLISIE LRNWIRRKIG VEVTVLEIVR ADSVRDLGVL
AQKKLAEK
