ID   SUBA_METRA              Reviewed;        2181 AA.
AC   E9F5E7;
DT   02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT   05-APR-2011, sequence version 1.
DT   03-AUG-2022, entry version 63.
DE   RecName: Full=Non-reducing polyketide synthase subA {ECO:0000303|PubMed:27189118};
DE            EC=2.3.1.- {ECO:0000269|PubMed:27189118};
DE   AltName: Full=Subglutinol biosynthesis cluster protein A {ECO:0000303|PubMed:27189118};
GN   Name=subA {ECO:0000303|PubMed:27189118}; ORFNames=MAA_07496;
OS   Metarhizium robertsii (strain ARSEF 23 / ATCC MYA-3075) (Metarhizium
OS   anisopliae (strain ARSEF 23)).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Clavicipitaceae; Metarhizium.
OX   NCBI_TaxID=655844;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ARSEF 23 / ATCC MYA-3075;
RX   PubMed=21253567; DOI=10.1371/journal.pgen.1001264;
RA   Gao Q., Jin K., Ying S.-H., Zhang Y., Xiao G., Shang Y., Duan Z., Hu X.,
RA   Xie X.-Q., Zhou G., Peng G., Luo Z., Huang W., Wang B., Fang W., Wang S.,
RA   Zhong Y., Ma L.-J., St Leger R.J., Zhao G.-P., Pei Y., Feng M.-G., Xia Y.,
RA   Wang C.;
RT   "Genome sequencing and comparative transcriptomics of the model
RT   entomopathogenic fungi Metarhizium anisopliae and M. acridum.";
RL   PLoS Genet. 7:E1001264-E1001264(2011).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=ARSEF 23 / ATCC MYA-3075;
RX   PubMed=25368161; DOI=10.1073/pnas.1412662111;
RA   Hu X., Xiao G., Zheng P., Shang Y., Su Y., Zhang X., Liu X., Zhan S.,
RA   St Leger R.J., Wang C.;
RT   "Trajectory and genomic determinants of fungal-pathogen speciation and host
RT   adaptation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:16796-16801(2014).
RN   [3]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=27189118; DOI=10.1038/ja.2016.54;
RA   Kato H., Tsunematsu Y., Yamamoto T., Namiki T., Kishimoto S., Noguchi H.,
RA   Watanabe K.;
RT   "New natural products isolated from Metarhizium robertsii ARSEF 23 by
RT   chemical screening and identification of the gene cluster through
RT   engineered biosynthesis in Aspergillus nidulans A1145.";
RL   J. Antibiot. 69:561-566(2016).
CC   -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC       that mediates the biosynthesis of the immunosuppressants subglutinols,
CC       meroterpenoids consisting of an alpha-pyrone (4-hydroxy-5,6-dimethyl-2-
CC       pyrone) moiety attached to a decalin core fused to a five-membered
CC       cyclic ether carrying a prenylside chain (PubMed:27189118). The first
CC       step of the pathway is the synthesis of the alpha-pyrone moiety by the
CC       polyketide synthase subA via condensation of one acetyl-CoA starter
CC       unit with 3 malonyl-CoA units and 2 methylations (PubMed:27189118). The
CC       alpha-pyrone is then combined with geranylgeranyl pyrophosphate (GGPP)
CC       formed by the GGPP synthase subD through the action of the
CC       prenyltransferase subC to yield a linear alpha-pyrone diterpenoid
CC       (PubMed:27189118). Subsequent steps in the subglutinol biosynthetic
CC       pathway involve the decalin core formation, which is thought to be
CC       initiated by the epoxidation of the C10-C11 olefin by the FAD-dependent
CC       oxidoreductase subE (Probable). The following cyclization cascade would
CC       be catalyzed by the terpene cyclase subB (Probable). Lastly, the FAD-
CC       dependent dehydrogenase subF probably catalyzes the five-membered
CC       cyclic ether formation to complete the formation of subglutinol A
CC       (Probable). Subsequent redox reactions appear to give rise to
CC       subglutinol C and D, however, it remains unclear which enzymes are
CC       responsible for these transformations (Probable).
CC       {ECO:0000269|PubMed:27189118, ECO:0000305|PubMed:27189118}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:27189118}.
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|PubMed:27189118}.
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DR   EMBL; ADNJ02000014; EFY96950.1; -; Genomic_DNA.
DR   RefSeq; XP_007823685.1; XM_007825494.1.
DR   AlphaFoldDB; E9F5E7; -.
DR   SMR; E9F5E7; -.
DR   EnsemblFungi; EFY96950; EFY96950; MAA_07496.
DR   GeneID; 19261782; -.
DR   KEGG; maj:MAA_07496; -.
DR   HOGENOM; CLU_000022_6_3_1; -.
DR   UniPathway; UPA00213; -.
DR   Proteomes; UP000002498; 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: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; 1.
PE   1: Evidence at protein level;
KW   Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW   Phosphoprotein; Transferase.
FT   CHAIN           1..2181
FT                   /note="Non-reducing polyketide synthase subA"
FT                   /id="PRO_0000451337"
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          1652..1673
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1982..2164
FT                   /note="Methyltransferase (CMeT) domain"
FT                   /evidence="ECO:0000255"
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;  239620 MW;  89DBF2DC481E70DC CRC64;
     MRVNTPSLLI CGPMISQADA AYLPQVRSSL VHNKDLSYLR EAVSELPNLW LRLVREEPSL
     GEIDVALFLD NLSQWVKGNS TQPTASRDSR NTQWAVLTVL VHIVEYMEYL DNFSSRDEDG
     CGHLDAHAAL LDHLHDGGIQ GLCIGLLTAL ALACAPSHAE IAKYGAVAVR LALCCGAYID
     LNEAKSPAKT ICVTTRWPGD DGDDKGDIDR KCDEQLQAIL DTYPDAYKSV QTDVSTVTIT
     TNEGDVLALL GELEKGGATS KRIDLHGRYH YGGNQAALLK LLQLSKALPM LQFPRGSRLV
     VPVRNNCSGS IVEDNTALHE MALRCILVEN AEWLKTISSS ISANTRQAQL LVLGPVNCVP
     RSLLLRSPQP ISLSVSGKAD NIYPDQSIAI IGSSCCFPGA ENPRQLWEFI RTKQTHGVVD
     AAGSFDCSFF RKSPREAEYM DPQQRLGLHL AQEALESGGY FSPSSSATKN VGCYLGISSC
     DYEDNVNSHP PTAYSFTGTA RAFASGRISH FFGLTGPSMV IDTACSSSGV AINTACRAIQ
     SGECTMALAG GINLISREAR TQENLAAASF LSPTGECRPF DSKANGYRRG EGGGLVLLKK
     LSSAVADGDV VLGVIAATAV NQSEGNKSIT LPSSESQTSL YQRVLESANL KPRHISYVEA
     HGTGTQKGDP IECQSIRTVF GGTVRPACRQ LHVGSIKSNI GHSEAASGIA ALLKVLQMLH
     HRVIPPQANF EELNPAISPL HDDNIEISRH TKPWEERFRA ALVNNYGASG TNAAMLVCQP
     PSIQHRLPLF PNRPCHYPIL LTSHSNESLQ LYCRNILRFI ENQNNVVSDE EVLANTAFHL
     AQRQDHSLSF RLTFSVSSIE ELKLKLQQQS TSQSYKDGPI QKHSAQPVVV VLAGQTGRRV
     RLSHEIYASS ELLQRHLGRC DRALQTMGFA SLFPGIFDTE PLEDLVQAHC MLFSLQYSVA
     MSWIDSGLKI DALVGHSLGQ LTALCISGML SLQDGLKLIS GRASLIQSKW GAECGAMLSV
     DADAETVQNL ADSLPAGYKV EIACYNSSQS HVVVGTKAAI TAFEKAADLR GVSLRRLAIS
     HGFHSEMIDC ILPDYNKLVQ GLVLHPPAIA IEPCSQSGHS WANATPEIIA RQSREPVYFA
     NAISRLEKRF GSCIWLEAGW GSAGVNMARR ALTHGPTRSL STHSFYPAAL GEPDSVKALA
     DTTINLWNAG IRVQFWLYHR SQTGSPAPLE LPLHPFMKSE YLLPVVKHSK KAQSEKDGQP
     IIQEKATLVS LIGKTQNAGV QTVEYSINQN SEEYSVYVRG RTVFEHLLAP VSMYIESATR
     AFRLLSTHKL VSFSTSASME LKNLKLHAPF GFDLQKSLRM ILRKLGEDAW EFRVESHPIH
     EKERGSVLQA TGVITLQEVY SHLAPHRPLL RRLYDRCEEL GKDVSASVVQ GDFIKKIINS
     VARYDDRYIG VRSITSKGFE TVAHVFEPEI ASQFTPTTPF NPLLLDNFLL IAEIQANNLG
     GVTPDEIYVG NGFDAATAYT NAEDSEPSTK GHWVGLYSFD HQENDGILCD IFIFCAERKI
     LSMTILGAKF QKIAISSLKR ALKTINGVPQ TSGGRTPSSS ITEFISGDDA SPCLPIPGAD
     KPIFIREDDF GFMTTSGHMD EENHLIPEYD VISGSSRSTS SSPPSLESRS QAMDTEEITE
     GAGSALFNLL SNHLNYPKGL SPDTPLGALG LDSLVAIQLQ SDIEQMFGKN SQLMDINESS
     TFSTLFHTIF PQQQTDQFGF VPLHDQTGKD RLESAVPLRL GYSHIKHAAP SFNDSLDRSN
     TLFIRQVPHA MDALKQNISS TIKAAGFHDF FSDVHPRQRS LVLAYIVHAF RELGCDIRSL
     EVGDELPSVQ FKPKYQNVMN RLFDILGSEG VINVLNKRYL GGLASFPERS AEDMHKAIMN
     DYPSYHPDHK LLHTTGARLA DCISGKVDPL QILFQNATSI KLLEDVYVKS PMFGTGNLLL
     GEFMNCLFSY NKTPDRLNHI RILEIGAGTG ATTQLVVDRL LACNVDFTYT FTDVSAALVA
     SAREKLTSRY GQHQRFDMEF ETLNIEKEPP ASFAQSYDLV ISANCIHATR DLRKSCSNIE
     KLLRKDGGVL CLLELTRPLE WLDCVFGLLD GWWRFDDHRT YALAGEQDWK TILLQSGFGH
     VDWTDDGSRE AQQLRLITAW R