DPMPA_MACPH
ID DPMPA_MACPH Reviewed; 2214 AA.
AC K2QVI8;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Non-reducing polyketide synthase dpmpA {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=dpmpA {ECO:0000303|PubMed:32286350}; ORFNames=MPH_09202;
OS Macrophomina phaseolina (strain MS6) (Charcoal rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Dothideomycetes incertae sedis; Botryosphaeriales; Botryosphaeriaceae;
OC Macrophomina.
OX NCBI_TaxID=1126212;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MS6;
RX PubMed=22992219; DOI=10.1186/1471-2164-13-493;
RA Islam M.S., Haque M.S., Islam M.M., Emdad E.M., Halim A., Hossen Q.M.M.,
RA Hossain M.Z., Ahmed B., Rahim S., Rahman M.S., Alam M.M., Hou S., Wan X.,
RA Saito J.A., Alam M.;
RT "Tools to kill: Genome of one of the most destructive plant pathogenic
RT fungi Macrophomina phaseolina.";
RL BMC Genomics 13:493-493(2012).
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 diterpenoid pyrones
CC (PubMed:32286350). The first step of the pathway is the synthesis of
CC the alpha-pyrone moiety by the polyketide synthase dpmpA via
CC condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units
CC and 2 methylations (Probable). The alpha-pyrone is then combined with
CC geranylgeranyl pyrophosphate (GGPP) formed by the GGPP synthase dpmpD
CC through the action of the prenyltransferase dpmpC to yield a linear
CC 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 dpmpE, and is followed by a
CC cyclization cascade catalyzed by the terpene cyclase dpmpB (Probable).
CC The short chain dehydrogenase/reductase dpmpG then oxidizes the 8S
CC hydroxy group to a ketone and the short chain dehydrogenase/reductase
CC dpmpH reduces the ketone to the 8R hydroxy group to yield higginsianin
CC B (PubMed:32286350). Higginsianin B is further methylated by the
CC methyltransferase dpmpI to produce the intermediate named FDDP B
CC (PubMed:32286350). The cytochrome P450 monooxygenase dpmpJ then
CC oxidizes the C-26 methyl to primary alcohol, producing the final
CC diterpenoid pyrone with a C-26 primary alcohol on the gamma-pyrone
CC moiety named FDDP C (PubMed:32286350). {ECO:0000269|PubMed:32286350,
CC ECO:0000305|PubMed:32286350}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|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 2 acyl-carrier protein (ACP) domains
CC that serve as the tether of the growing and completed polyketide via
CC its phosphopantetheinyl arm. {ECO:0000305}.
CC -!- BIOTECHNOLOGY: Diterpenoid pyrones display various biological
CC activities and FDDP C shows anti-cancer and anti-HIV activities
CC (PubMed:32286350). FDDP C shows also inhibitory activity of 42-mer-
CC amyloid beta aggregation that is involved in the pathogenesis of
CC Alzheimer's disease (PubMed:32286350). {ECO:0000269|PubMed:32286350}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AHHD01000387; EKG13736.1; -; Genomic_DNA.
DR AlphaFoldDB; K2QVI8; -.
DR SMR; K2QVI8; -.
DR STRING; 1126212.K2QVI8; -.
DR EnsemblFungi; EKG13736; EKG13736; MPH_09202.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_6_3_1; -.
DR InParanoid; K2QVI8; -.
DR OrthoDB; 93381at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000007129; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
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; -; 2.
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; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
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; 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; 2.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
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.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2214
FT /note="Non-reducing polyketide synthase dpmpA"
FT /id="PRO_0000451526"
FT DOMAIN 1620..1695
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1722..1802
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 75..178
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 375..787
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 888..1184
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1265..1560
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1698..1728
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1805..1827
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1958..2210
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1809..1827
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 532
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 974
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1654
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1762
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2214 AA; 240809 MW; EE67D92341960371 CRC64;
MSVELPSLVV CGPQLEEIPD ATYLARLRSS LLHDPYLRSL KQEALELHEM WPLLSATEPS
LARFDAAPLL HSFAEWIRTG DSHVLRLAGG TLRNTQLALL TVLAHLLEYT TYLQHRHHHD
HAQSEHAVLT AVHDGGVQGL SIGVLSAIAI SCSQSRMHLA RYGAVALRLA VCAGAWKDLD
EMHAAEPPVC LEARWEGGGA RAFKAVLDSY PQAYAHVRED ASNATVIVPE SSAAAMARKL
EEDGIEARQV GLQGLSHRPD HFAACQKLFN LCSSLPMLRF PEHCHPLVPL TRNGNAEAVD
DGASLHEMAL RCILLEKPDS AAITAQCVAA ISRQAGEPRV LLLGRVECIP RSVPARLIRP
MAAGHSLYVY PDESIAIVGA SCRFAGSETP AGFWDTLRER RSTLGKAPVW RGYGSEEEPF
WGNFLASAGA FDHAFFRKSP REAAYMDPQH RLALHLAYEA LESGGYFNPA AGTQTYDVGC
YVGVYSSDYE DNVNARPPTP FSFTGTARAF ASGRISQFFG WTGPSLIVDT ACSSSGVAIH
TACKAIQSGE CTMALAGGVN LMTSPKSHQN LAAASLMSRT GQCKPFDASA DGYCRGEGGG
FVLLKRLSSA VADNDRVLGV LAASAINNSK GSLTITAPSL ESQAALYQSV LRKAGMQPDQ
VSYVEAHGTG TQKGDPVECH SLRRVFGRSS RNSPPLRFGS VKGNIGHSEG ASGVASLVKV
LLMLQHGLIA PQANFSVLNP AAPNLEEANM EIPLYLQPWD AAFRAACVNN YGAAGNNTAM
IVCQPPATQP VSRPSSVQKR HQYPFMLTAH SDASLRQHCR ILLQFVEDQQ AWAGDDLLAS
LAFHLAQRQS HQLGYRTAFS ARSIDDLKAR LGEQNTQTRG NCNPVVLVFA GQTGHRPRLS
EEAYHSSFLL QHHLDRCDRT LQTLGLRGLF PQVFGTQAVD DLVDLHCMLF SIQYATAAAW
IDAGLDVRKL VGHSLGQLTA LCVARVLTLR DALKMISGRA ALIQSKWGPE QGCMLSVDSD
AVTVRALIDS MASEEKVEIA CYNAPSSHVV VGKAGATAAF ESAALSAGVR TKRLAITHAF
HSPMVDSIME DYESLLRELQ FHSPTIPIEP CEQSGGSWEN LTPERVARQS RAPVYFGAAV
SRVERELGSC VWLEAGAGPA GVTMARRAAS SSSHAFLSAR LGSPDAMDSL ADTTLSLWRE
GVRVQFWPFH PWQRHCFRLL ELPPYQFETT HHWLPFASAP ESAAQQPTTA NDVAPQLVSV
VRSSGGADPE AAEFTINQHS EEYALFVGGR TVLGHALSPP SVYLESAARA LGLVSAAAGG
PAALPPHFEQ VQLHAPLGID PRRRIRLRLQ KHNTSAWEFV FDSQAPALDG GQTFQLQASG
IIKSQEQDRA VAGPYRPLLR RLIDHERCRV LLEDSGASVV QGAFVKNILG RVASYEDSYF
GIRSITSKGH EAVGVVDVPE IAHQRCAETR VNPPLLDNFM LVAEMHAGNL DACGSDQMYV
CNGFDALVPH SNDGSLRGPF TVYSKLERES DRVFVGDVFV LTGGQKTLSL AILGARFSKV
PVRSLQRALE AANGSPNVRT AEALDHSAVA IEARDSALTS PPIRPHAPPS SDAVSTISLN
EVKTTTERVI SETTGVPRER INDATLLGDL GVDSLMATEL QVRFSDVLHV DLAIGTLCEH
GMTAGRLCQE IHSRLSGVPQ LSPHDTDRSS DLSAGQPPST PKASTQEQEH FIVELSKLLA
EHLNCSPDIP PETPLALMGL DSLLAIQLAS DMESRFGKKS SPMNIDENTT FSDLCRVLSG
ADLPGFPRTS DNRRSEEGSV GHVGPEKSEA SFFREREDVI KLEFDRAKQR YGVFSEQAGL
AGFYARVYPR QMALVLAYIV EAFRTLGCDV ATLRAGERLP PIPHEPRYEK LVRRYLQLLE
DAGLITSSGE HPPAHLRTAK ALEHAESSRL HRAILADFPA YRPDHRLLQL TGPRLADCVS
GKVDPLQLLF HGPASRQLLE AFYVSSPMFA TATRMMSEFV GQLLRKHGGC SERLRVLEVG
AGTGATTQQL LDQLVASGAA FTYTFTDVSS SLVAAARRRL EARYAAAGHE MHFAVLDIER
PPPQRLLHSQ DLVVASNVLH ATRSLSDTCS NVQRLLRPGC GVLCLLELTR PLPWLDCVFG
LLDGWWRFAD SRTYPLVDEW RWKACLLNAG FRHVDWTDDE SREADLFRWI LALA
