ID   DPMAA_METAN             Reviewed;        2181 AA.
AC   P9WEX6;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   02-DEC-2020, sequence version 1.
DT   03-AUG-2022, entry version 8.
DE   RecName: Full=Non-reducing polyketide synthase dpmaA {ECO:0000303|PubMed:32286350};
DE            EC=2.3.1.- {ECO:0000305|PubMed:32286350};
DE   AltName: Full=Diterpenoid pyrone biosynthesis cluster protein A {ECO:0000303|PubMed:32286350};
GN   Name=dpmaA {ECO:0000303|PubMed:32286350}; ORFNames=MANI_006324;
OS   Metarhizium anisopliae (Entomophthora anisopliae).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Metarhizium.
OX   NCBI_TaxID=5530;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=25263348; DOI=10.1186/1471-2164-15-822;
RA   Staats C.C., Junges A., Guedes R.L., Thompson C.E., de Morais G.L.,
RA   Boldo J.T., de Almeida L.G., Andreis F.C., Gerber A.L., Sbaraini N.,
RA   da Paixao R.L., Broetto L., Landell M., Santi L., Beys-da-Silva W.O.,
RA   Silveira C.P., Serrano T.R., de Oliveira E.S., Kmetzsch L., Vainstein M.H.,
RA   de Vasconcelos A.T., Schrank A.;
RT   "Comparative genome analysis of entomopathogenic fungi reveals a complex
RT   set of secreted proteins.";
RL   BMC Genomics 15:822-822(2014).
RN   [2]
RP   FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RX   PubMed=32286350; DOI=10.1038/s41467-020-15664-4;
RA   Tsukada K., Shinki S., Kaneko A., Murakami K., Irie K., Murai M.,
RA   Miyoshi H., Dan S., Kawaji K., Hayashi H., Kodama E.N., Hori A., Salim E.,
RA   Kuraishi T., Hirata N., Kanda Y., Asai T.;
RT   "Synthetic biology based construction of biological activity-related
RT   library of fungal decalin-containing diterpenoid pyrones.";
RL   Nat. Commun. 11:1830-1830(2020).
CC   -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC       that mediates the biosynthesis of the diterpenoid pyrones subglutinols
CC       A and B (PubMed:32286350). The first step of the pathway is the
CC       synthesis of the alpha-pyrone moiety by the polyketide synthase dpmaA
CC       via condensation of one acetyl-CoA starter unit with 3 malonyl-CoA
CC       units and 2 methylations (Probable). The alpha-pyrone is then combined
CC       with geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase
CC       dpmaD through the action of the prenyltransferase dpmaC to yield a
CC       linear alpha-pyrone diterpenoid (Probable). Subsequent steps in the
CC       diterpenoid pyrone biosynthetic pathway involve the decalin core
CC       formation, which is initiated by the epoxidation of the C10-C11 olefin
CC       by the FAD-dependent oxidoreductase dpmaE, and is followed by a
CC       cyclization cascade catalyzed by the terpene cyclase dpmaB (Probable).
CC       The dehydrogenase dpmaF is then involved in tetrahydrofuran (THF) ring
CC       formation at the C5 unit to complete the formation of subglutinols A
CC       and B (PubMed:32286350). {ECO:0000269|PubMed:32286350,
CC       ECO:0000305|PubMed:32286350}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:32286350}.
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; a methyltransferase (CMeT) domain
CC       responsible for methylations; and an acyl-carrier protein (ACP) that
CC       serves as the tether of the growing and completed polyketide via its
CC       phosphopantetheinyl arm. {ECO:0000305}.
CC   -!- BIOTECHNOLOGY: Diterpenoid pyrones display various biological
CC       activities and subglutinol A shows insecticidal and anti-HIV
CC       activities. {ECO:0000269|PubMed:32286350}.
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DR   EMBL; JNNZ01000128; KFG81921.1; -; Genomic_DNA.
DR   AlphaFoldDB; P9WEX6; -.
DR   SMR; P9WEX6; -.
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: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; -; 2.
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; IPR041068; HTH_51.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR   InterPro; IPR042104; PKS_dehydratase_sf.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR032088; SAT.
DR   InterPro; IPR016039; Thiolase-like.
DR   Pfam; PF00698; Acyl_transf_1; 1.
DR   Pfam; PF18558; HTH_51; 1.
DR   Pfam; PF00109; ketoacyl-synt; 1.
DR   Pfam; PF02801; Ketoacyl-synt_C; 1.
DR   Pfam; PF08242; Methyltransf_12; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   Pfam; PF16073; SAT; 1.
DR   SMART; SM00827; PKS_AT; 1.
DR   SMART; SM00825; PKS_KS; 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; 2.
PE   1: Evidence at protein level;
KW   Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW   Phosphoprotein; Transferase.
FT   CHAIN           1..2181
FT                   /note="Non-reducing polyketide synthase dpmaA"
FT                   /id="PRO_0000451525"
FT   DOMAIN          1677..1753
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          74..180
FT                   /note="N-terminal acylcarrier protein transacylase domain
FT                   (SAT)"
FT                   /evidence="ECO:0000255"
FT   REGION          388..782
FT                   /note="Ketosynthase (KS) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          891..1193
FT                   /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1276..1573
FT                   /note="Product template (PT) domain"
FT                   /evidence="ECO:0000255"
FT   REGION          1587..1618
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1652..1675
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1982..2164
FT                   /note="Methyltransferase (CMeT) domain"
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        1587..1606
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        525
FT                   /note="For beta-ketoacyl synthase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   ACT_SITE        977
FT                   /note="For acyl/malonyl transferase activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT   MOD_RES         1713
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2181 AA;  239929 MW;  EC6BE40099695C13 CRC64;
     MRVNTPSLLI CGPMISQADA AYLPQVRSNL VHNKNLSYLR EAVSELPNLW LRLVREEPSL
     GEIDVALFLD NLSQWVKGNS TQPTASRDSR NTQWAVLTVL VQIVEYMEYL DNFSSRDEDG
     CGHLDAHAAL LDHLHEGGIQ GLCIGLLTAL ALACAPSHTE IAKYGAVAVR LALCCGAYID
     LNEAKSPAKT ICVTTRWPGD DGDDKGDIDR KCDEQLQAIL DKYPDAYKSV QTDVSTATIT
     SNEGNVLALL TELEKDGAIS KRIDLHGRYH YGGNQAALDK LLQLSSALPM LQFPRRSRLV
     VPVRNNCNGN IVEDNTALHE MALRCILVEN AEWFKTISSS ISANTRQAQL LVLGPVNCVP
     RSLLLRSPQP ISLSVSGKAD NIYPDQSIAI IGSSCCFPGA ENPRQLWEFI RTKQTRGVVD
     AAGSFDCSFF RKSPREAEYM DPQQRLGLHL AQEALESGGY FSPSSSATKN VGCYLGISSC
     DYEDNVNSHP PTAYSFTGTA RAFASGRISH FFGLTGPSMV IDTACSSSGV AINTACRAIQ
     SGECTMALAG GINLISREAR TQENLAAASF LSPTGQCRPF DSKANGYRRG EGGGLVLLKK
     LSSAVADGDV VLGVIAATAV NQSEGNKSIT LPSSESQTSL YRRVLESANM KPRHISYVEA
     HGTGTQKGDP IECQSIRTVF GGTLRPACRQ LHVGSIKSNI GHSEAASGIA ALLKVLQMLH
     HRVIPPQANF EELNPAISPL HDDNIEISRQ TKPWEERFRA ALVNNYGASG TNAAMLVCQP
     PSIQHSLPLF PNRPCHYPIL LTSHSNESLQ LYCRNILRFI ENQNNVDSDE EVLANTAFHL
     AQRQDHSLSF RLTFSVSSIE ELKSKLQQQS TSQSYKDGPI QKHSGQPVVV VLAGQTGRRV
     RLSHEIYASS ELLQRHLGRC DRALQTMGFT SLFPGIFDTE PVEDLVQAHC MLFSLQYSVA
     MSWVDSGLKI DALVGHSLGQ LTALCISGML SLQDGLKLIS GRASLIQSKW GAECGAMLSV
     DADAETVQNL ADSLPAGYKV EIACYNSSQS HVVVGTKAAI TAFEKAADLR GVSLRRLAIS
     HGFHSEMIDG ILPDYNKLVQ GLVLHPPAIA IEPCSQSGHS WANATPEIIA RQSREPVYFA
     NAISRLEKRF GSCIWLEAGW GSAGVNMARR ALTHGPTRSL STHSFYPAAL GEPDSVKALA
     DTTINLWNAG IRVQFWLYHR SQTGSPAPLE LPLHPFMKSE YLLPVVKHSK KAQNEKVGQP
     VIQEKATLVS LIGKTQNAGV QTVEYSINQN SEEYSVYVRG RTVFEHFLAP VSMYIESATR
     AFRLLSTHKL VSFSTSASME LKNLKLHAPF GFDLQKSLRM ILRKLGEDAW EFRVESHPIH
     EKERGSILQA TGVITLQEVY SHLAPHRPVL RRLYDRCEEL GKDVSASVVQ GDFIKKIINS
     VARYDDRYIG VRSITSKGFE TVAHVFEPEI ASQFNPTSPF NPLLLDNFLL IAEIQANNLG
     GVTPDEIYVG NGFDAATAYT NAEDSEPSTK GHWVGLYSFD HQENDGILCD IFIFCAERKI
     LSMTILGAKF QKIAISSLKR ALKTINGVPQ TSGGRTPSSS ITEFISGDDA SPCPPIPGAD
     KPIFIREDDF GSMTTSGHMD EENHLIPEYD VISGSSRSTS SSPPSLESRS QAMETEEITE
     GAGSALFNLL SNHLNYPKGL SPDTPLGALG LDSLVAIQLQ SDIEQMFGKN SQLMDINESS
     TFSTLFHTIF PQQQTDQFGF VPLHDQTGKD RLESAVPLRL GYSHIKHAAP SFNDSLDRSN
     TLFIRQVPHA MDALKQNISS TIKAAGFHDF FSDVHPRQRS LVLAYIVQAF RELGCDIRSL
     RVGDELPSVQ FKPKYQNLMN RLFDILGSEG VINVLNKRYL GGLASFPERS AEDMHKAILN
     DYPSYHPDHK LLHTTGARLA DCISGKVDPL QILFQNAASI KLLEDVYVKS PMFGTGNLLL
     GEFMNCLFSY NKTPDRLNHI RILEIGAGTG ATTQLVVDRL LACNVDFTYT FTDVSAALVA
     SAREKLTTRY GQHQRFDMEF ETLNIEKEPP ASFAQSYDLV ISANCIHATR DLRKSCSNIE
     KLLRKDGGML CLLELTRPLE WLDCVFGLLD GWWRFDDHRT YALAGEQDWK TILLQSGFDH
     IDWTDDGSRE AQQLRLITAW R