OLCA_PENCN
ID OLCA_PENCN Reviewed; 2443 AA.
AC P9WEQ0;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 1.
DT 03-AUG-2022, entry version 4.
DE RecName: Full=Non-reducing polyketide synthase olcA {ECO:0000303|PubMed:30090271};
DE EC=2.3.1.- {ECO:0000269|PubMed:30090271};
DE AltName: Full=15-deoxyoxalicine B biosynthesis cluster protein A {ECO:0000303|PubMed:30090271};
GN Name=olcA {ECO:0000303|PubMed:30090271};
OS Penicillium canescens.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5083;
RN [1]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=30090271; DOI=10.1039/c5sc01965f;
RA Yaegashi J., Romsdahl J., Chiang Y.M., Wang C.C.C.;
RT "Genome mining and molecular characterization of the biosynthetic gene
RT cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium
RT canescens.";
RL Chem. Sci. 6:6537-6544(2015).
RN [2]
RP ERRATUM OF PUBMED:30090271.
RX PubMed=30123464; DOI=10.1039/c6sc90012g;
RA Yaegashi J., Romsdahl J., Chiang Y.M., Wang C.C.C.;
RT "Correction: Genome mining and molecular characterization of the
RT biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine
RT B, in Penicillium canescens.";
RL Chem. Sci. 7:2440-2440(2016).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of 15-deoxyoxalicine B
CC (PubMed:30090271). The first step of the pathway is the synthesis of
CC nicotinyl-CoA from nicotinic acid by the nicotinic acid-CoA ligase olcI
CC (PubMed:30090271). Nicotinyl-CoA is then a substrate of polyketide
CC synthase olcA to produce 4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one
CC (HPPO) which is further prenylated by the polyprenyl transferase olcH
CC to yield geranylgeranyl-HPPO (PubMed:30090271). Geranylgeranyl
CC pyrophosphate is provided by the cluster-specific geranylgeranyl
CC pyrophosphate synthase olcC (PubMed:30090271). The FAD-dependent
CC monooxygenase olcE catalyzes the epoxidation of geranylgeranyl-HPPO and
CC the terpene cyclase olcD catalyzes the cyclization of the terpenoid
CC component, resulting in the formation of the tricyclic terpene moiety
CC seen in predecaturin E (PubMed:30090271). The cytochrome P450
CC monooxygenase then catalyzes the allylic oxidation of predecaturin E,
CC which is followed by spirocylization with concomitant loss of one
CC molecule of water to form decaturin E (PubMed:30090271). Decaturin E is
CC the substrate of the cytochrome P450 monooxygenase olcJ which
CC hydroxylates it at the C-29 position to form decaturin F
CC (PubMed:30090271). The short-chain dehydrogenase/reductase olcF may
CC catalyze the oxidation of decaturin F to generate the 29-hydroxyl-27-
CC one intermediate, and subsequent hemiacetal formation probably leads to
CC the formation of decaturin C (Probable). The dioxygenase olcK may be a
CC peroxisomal enzyme that catalyzes the hydroxylation of decaturin C into
CC decaturin A once decaturin C is shuttled into the peroxisome by the MFS
CC transporter olcL (Probable). Finally the cytochrome P450 monooxygenase
CC olcB catalyzes the oxidative rearrangement to yield 15-deoxyoxalicine B
CC (PubMed:30090271). In the absence of olcJ, decaturin E may be shunted
CC to a pathway in which it is oxidized to a ketone, possibly by olcF, to
CC form decaturin D, which undergoes further allylic oxidation to yield
CC decaturin G (PubMed:30090271). Moreover, in the absence of oclK or
CC oclL, oclB can convert decaturin C into 15-deoxyoxalicine A
CC (PubMed:30090271). {ECO:0000269|PubMed:30090271,
CC ECO:0000305|PubMed:30090271}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 malonyl-CoA + nicotinyl-CoA = 4-hydroxy-6-(pyridin-3-
CC yl)-2H-pyran-2-one + 2 CO2 + 3 CoA; Xref=Rhea:RHEA:64336,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:149703, ChEBI:CHEBI:149707;
CC Evidence={ECO:0000269|PubMed:30090271};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64337;
CC Evidence={ECO:0000269|PubMed:30090271};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30090271}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm. {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of 15-deoxyoxalicine B.
CC {ECO:0000269|PubMed:30090271}.
CC -!- MISCELLANEOUS: The 15-deoxyoxalicine B cluster is a rare cluster that
CC contains its own geranylgeranyl pyrophosphate synthase (olcC), in
CC contrast to other related clusters which rely on a FPP/GGPP synthase
CC localized outside of the cluster. {ECO:0000269|PubMed:30090271}.
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DR SMR; P9WEQ0; -.
DR UniPathway; UPA00213; -.
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; 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; 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; 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; Transferase.
FT CHAIN 1..2443
FT /note="Non-reducing polyketide synthase olcA"
FT /id="PRO_0000453885"
FT DOMAIN 2359..2434
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 5..386
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 550..885
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 989..1497
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1771..2159
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 178
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 645
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2394
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2443 AA; 267873 MW; 3420FF7EE5DB7FBC CRC64;
MVSAIEPIAI VGTGCRFPGN CSSSARLWEL LRSPQNVASK VPADRFNVDA FYHPDGTHHG
TTNVKEGYFL KEDVRAFDAS FFNISPTEAA SMDPQQRLLL ETVYESLESA GLQMEALQGS
STGVFCGFLR NDYSQIQTTD RDALPAYMVT GNSPSIMANR VSYFFDWKGP SFGMDTGCSS
SLLAVHLAVE ALHRGDCSMA MAVGSNLILS PTPFIADSAT GMLSPTGRSR MWDESADGYA
RGEGVAAVVL KRLSDALADG DEIECLIRAT AANADGRTMG ITMPNGNAQQ ELIHNTYTKA
GLDPKNSEGR CQYFEAHGTG TQAGDPQEAG AIFNAFFGDS PTTDLKAEEK LYVGSIKTVI
GHTEATAGLA GLIKASLCLQ HSEIVPNMLL ERLNPKLSSF MSCLHVPTEN MPWPKLPAGA
PRRASVNSFG FGGANVHAIL ESYDAPATSP PTHSLPFILP FTFSAASERS LGAVLQQHGR
YLQDAKEEHL LDLAATLGNR RSVFSHRVNL TASSLEDLRS KVQHEIEQNT TEYSSTVICR
SKARSHSVLG VFTGQGAQWP QMGLDLIMAC PEARMWIDEM QESLNRLPAE YRPNFVMMDE
LSKPKDKSRV HEAAISQPLR TAIQIIQVNF LRALGISFTA VVGHSSGEVA AAYAAGLLNS
SDAIRIAYLR GNVAKYAGST GQQGAMMAVG LSGGDADAIC SQESYVGRVS VAAYNSPSSV
TLSGDQDVLT ELEWLLRSLG RQVKVLRVDT AYHSHHMLPC AEPYLKALKK CNISIQRPQT
SRWFSSVFNG REMMSDDDSL QGEYWKENMV HSVEFSQAMA MAVDQISGPD LIMEVGPHPA
LKGPAIETLS TIQTDTQIPY IGLTKRDSSS IECFAAAIGS LWTYLESGCM DLPKYVSLFD
PAYHLKFVKD LPSYPFDHRE QFWAESRLSK AVSHRSNPPN CLLGVLSPDS GKEEQVWRGY
LRRDSLQWLI GYEIRSLPLF PPSGYISLAL ESAKLIAGQE QLQLLEVQDL AIENDLPIAD
NTTGVEIVFK VGSLRTNGKH IHGTFNCQAG VSGKLISCAS GVLTMTLGSA DAAALPARRS
SLPDMRAVDI EDFYSALTRL GHLYSEDFKC LKALSRRRDG ACGSALNSIE RKPGSPLLHP
ATAETSFQVL MAALENPSNS QSSILYRPTL IRRTVINLAL CDSPELMLDA SILHVEPEGI
HGVVDVFNST GQGVMQLEGV HLVPLLEDLA DVHSATLFSE TVWGPVKLDA TLGASDCAPN
VASSLELRER LTFLHLRNIG DQLSLKARQN LDKPRAFFVA WMDHVLAAVR DNDHPTCRSE
WLGENLQHFL SIDHGLHQSE LLAMDKICRS ISARLLCMGD TQEDVFVNEA LAEYYQTSRE
FSSLCDRLVK VVGQILFLFP RLNVLEVRRG TDLVTKRLLR EFGHAFHSYT CTDTSDVPPA
RKESQNAQSK RLISYTSLDL CDDIVVQGYQ EHSQDLVVIT NSGHGSCSLP VTISNMRRLL
KPGGYIVIIE TTNPTLVYPK FFSGTPQNWK ESVRTRSEWN TLLLSGGFSG IDTANPAHEA
AILNMSLFVS QAVDDQIQLL RSPLSMCSAV ANQDLFFVCE TNDDMEPLRN SLYGLLKPRF
NHIVSAENLD AMEFEGFCAP TVLVLTYKND SWFQTITNEQ CRASIQKTFK AAGKLLWVTV
DAQVDPYRAM TNGMLRSISL EYPSVTFQHL EIPNPNAVSF KILATALMRL VHTKFENNCR
LSGVVTATEP EVRYVDGAFL VPRQQTSSFP NKRYLAHTHV VDGDVGIEHI LIEPTKPERL
DSPVRVVAHS TTSSYSPQSP RVTLRVQYST LRAVRVDTAG YLYLVVGRDV QSQSRFLAVT
DKNAGLISID VLRTRPIPSW IPEGQEDDLL LFITCALIAE QILSEVHPGT SLLVHEPDSA
LYQALATAAP LHMIEVFFST SKSPPANGMM FIHKNVSSLA LSRQLPSDLS VIAASASSSG
TLFRRATSLL RKDIRQVDID NFFRASPQTR QVQVSDLRGI AHALKQTRAL HDTRASVTEV
DAISGHPGAL DNLEIVDWTA SKPIPAQIRS ASSHVSLSAA KSYLLLAMQK DLAVSVSEWM
VARGARHVVL AGTASDINVD KGWVEEMASR GACIHCLPTD ISERQSVLLL ERFTCALPPA
GGIIYGALAR LPADNLFPMA RQNRDVSPIT SLLESSILLD ELYNHPAMDF FIFVGSLSGQ
FNHANMVECA AASEFSSALI RRRRSRSFSG SIVFMSQIPD PKSESKFLGE KYLSEHDLDE
VFAESILAGD PNSTGNHEIT AGLRPIKPEH TEMSWNRIPK MWNFVQHLAE FNSVSPSHSE
VITMSVLLER ATSQREVTEI LTSHLLTQLR TKLGLSTEAV LVPETQLSEL GVDSLVAADL
RTWFLKELSV DVPILFMLSG SSIQEITSSA AAKLDASRIP HAQ
