CNSI_PENEN
ID CNSI_PENEN Reviewed; 2363 AA.
AC A0A0A2JW91;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 04-FEB-2015, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Highly reducing polyketide synthase cnsI {ECO:0000303|PubMed:25571861};
DE EC=2.3.1.- {ECO:0000269|PubMed:25571861};
DE AltName: Full=Communesin biosynthesis cluster protein I {ECO:0000303|PubMed:25571861};
GN Name=cnsI {ECO:0000303|PubMed:25571861}; ORFNames=PEX2_055430;
OS Penicillium expansum (Blue mold rot fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=27334;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MD-8;
RX PubMed=25338147; DOI=10.1094/MPMI-09-14-0261-FI;
RA Ballester A.R., Marcet-Houben M., Levin E., Sela N., Selma-Lazaro C.,
RA Carmona L., Wisniewski M., Droby S., Gonzalez-Candelas L., Gabaldon T.;
RT "Genome, transcriptome, and functional analyses of Penicillium expansum
RT provide new insights into secondary metabolism and pathogenicity.";
RL Mol. Plant Microbe Interact. 28:232-248(2015).
RN [2]
RP IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RX PubMed=25571861; DOI=10.1002/anie.201411297;
RA Lin H.C., Chiou G., Chooi Y.H., McMahon T.C., Xu W., Garg N.K., Tang Y.;
RT "Elucidation of the concise biosynthetic pathway of the communesin indole
RT alkaloids.";
RL Angew. Chem. Int. Ed. 54:3004-3007(2015).
RN [3]
RP FUNCTION.
RX PubMed=26963294; DOI=10.1021/jacs.6b01413;
RA Lin H.C., McMahon T.C., Patel A., Corsello M., Simon A., Xu W., Zhao M.,
RA Houk K.N., Garg N.K., Tang Y.;
RT "P450-mediated coupling of indole fragments to forge communesin and
RT unnatural isomers.";
RL J. Am. Chem. Soc. 138:4002-4005(2016).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of communesins, a prominent class of
CC indole alkaloids with great potential as pharmaceuticals
CC (PubMed:25571861). Communesins are biosynthesized by the coupling of
CC tryptamine and aurantioclavine, two building blocks derived from L-
CC tryptophan (PubMed:25571861). The L-tryptophan decarboxylase cnsB
CC converts L-tryptophan to tryptamine, whereas the tryptophan
CC dimethylallyltransferase cnsF converts L-tryptophan to 4-dimethylallyl
CC tryptophan which is further transformed to aurantioclavine by the
CC aurantioclavine synthase cnsA, probably aided by the catalase cnsD
CC (PubMed:25571861). The cytochrome P450 monooxygenase cnsC catalyzes the
CC heterodimeric coupling between the two different indole moieties,
CC tryptamine and aurantioclavine, to construct vicinal quaternary
CC stereocenters and yield the heptacyclic communesin scaffold
CC (PubMed:26963294). The O-methyltransferase cnsE then methylates the
CC communesin scaffold to produce communesin K, the simplest characterized
CC communesin that contains the heptacyclic core (PubMed:25571861). The
CC dioxygenase cnsJ converts communesin K into communesin I
CC (PubMed:25571861). Acylation to introduce the hexadienyl group at
CC position N16 of communesin I by the acyltransferase cnsK leads to the
CC production of communesin B. The hexadienyl group is produced by the
CC highly reducing polyketide synthase cnsI, before being hydrolytically
CC removed from cnsI by the serine hydrolase cnsH, converted into
CC hexadienyl-CoA by the CoA ligase cnsG, and then transferred to
CC communesin I by cnsK (PubMed:25571861). Surprisingly, cnsK may also be
CC a promiscuous acyltransferase that can tolerate a range of acyl groups,
CC including acetyl-, propionyl-, and butyryl-CoA, which lead to
CC communesins A, G and H respectively (PubMed:25571861). The roles of the
CC alpha-ketoglutarate-dependent dioxygenases cnsM and cnsP have still to
CC be determined (PubMed:25571861). {ECO:0000269|PubMed:25571861,
CC ECO:0000269|PubMed:26963294}.
CC -!- PATHWAY: Alkaloid biosynthesis. {ECO:0000269|PubMed:25571861}.
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:0000305|PubMed:25571861}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the biosynthesis of communesin B and
CC leads to the exclusive formation of communesin A.
CC {ECO:0000269|PubMed:25571861}.
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DR EMBL; JQFZ01000090; KGO59702.1; -; Genomic_DNA.
DR RefSeq; XP_016600815.1; XM_016742817.1.
DR AlphaFoldDB; A0A0A2JW91; -.
DR SMR; A0A0A2JW91; -.
DR EnsemblFungi; KGO59702; KGO59702; PEX2_055430.
DR GeneID; 27678236; -.
DR HOGENOM; CLU_000022_31_0_1; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000030143; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase 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:0044550; P:secondary metabolite biosynthetic 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 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; IPR011032; GroES-like_sf.
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; 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; 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; 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; 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 Multifunctional enzyme; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2363
FT /note="Highly reducing polyketide synthase cnsI"
FT /id="PRO_0000446464"
FT DOMAIN 2279..2357
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:25571861"
FT REGION 17..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25571861"
FT REGION 546..854
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25571861"
FT REGION 938..1224
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25571861"
FT REGION 1669..1976
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25571861"
FT REGION 2001..2177
FT /note="Catalytic ketoreductase (KRc) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25571861"
FT ACT_SITE 187
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 638
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 970
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2317
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2363 AA; 256832 MW; 47E5F6DE412CFB8C CRC64;
MSTETQPEMA STPPEPIAII GMSCRLSGEA SSVDGFWDML RNGRTGHGRV PSSRYEASAW
YHPNQDRKGG INHDSGFFLE EDPSRFDAPF FSITAKEAAG MDPTQRLLLE VAYETFENSG
VPMESLPGSR TGVFTGCMTN DYELLSTGDL YNMPHNAATG NARAMLANRL SWFFDLRGPS
IMLDTACSSS LTALHLASKS LRDGECEMAL VSGASLILHP NFTQRLSSMH MLSPDGISHS
FDASANGYGR GEGFAAVLLK PLRTALADND AIRAIIRATG INQDGRTPGI TMPSRQAQAG
LIRALYGPGL PSLQETAFFE AHGTGTKVGD PTELSAIGEC LMGAETSTND RLYVGSVKGN
IGHTEGAAGV ASLIKVVLCL ENDMLVPNAG FSKLNSNIHL DKWLLRLSDK TIRWPSHLPR
RASINSFGFG GSNAHAIVES ASTYLERPAA LLSGLDKGEP QIVVFSTHDK TGIDRVAAKW
GPFLQAQIDA EQNISFRDIA YTMYARRSQL SFRSFAVAGS LGQLRDALQQ GLPHFLRANG
TAHANLAFVF TGQGAQWAQM GVELLQVTSF RESITRSEQI LSSLGCPWNL FEEIQVEAAT
SRMNQPDRSQ SICCALQIAL VNLLASWGVH PKATVGHSSG EIGAAYAAGF ITQEDAIRIA
YFRGLCSLQV ACHGRAGAML AANLSLPDAQ TYLQGVPPRS VVVACVNGPK SVTLSGDADR
IDQLEKQLQA DGLFARKLRV ETAYHSPHMN MVAEGYRHDL QDIQPAKCGE SSIAMFSSVT
KERVYATDMT ADYWVRNLVS PVEFLSAVTS LANMTEASQY RHRAVAVKWS AFLEIGPHEA
LKGPFLQVLK SINAGLSTVP YHALVRRHAD ALQTTLNVAG LLWCIGIPID IEAVNSSINT
AVPQLMHNLP SYPWNHQGSF WHEPVASARL RKRREPHHDL LGSPMDFQND TEPRWRNFLR
VSDIPWLADH VVADSILFPA AGMIVMVAEA GRILANTSLR LEGIEFNDLA FLQGLVIPDD
DRGVETVLHV APYHELAEWY EFTLFSLPED GPWVRHATGT FTLHYDARGV PLNVEEWGLS
VERFRKIQTA ECETNRDAVY EWLSQTGGVT MGPAFQSVSR AAFCTEENRL WIEGEVTDTR
TMMPSEYASP CFIHPTSLDT LFQAAVLSCS DALGNQNAKI PVGVDRLYLS TTWDLQQGDY
FSVHTETCLN DGDSRLDSIA SDVSWSQPRV VLKGVRLGPV PMSKVPSTST TAGVDSGTSR
FSSIVWAQHL ESPTSPALAG HDRDGQLTDW VRDICYTYGN ACALVVTQPS WKSPAMTSIQ
TVRPQLGSRP CLQGLTIVIV GLDKAADEFA TAVTRLMPGA QVKQIAALQD FSPSTFNESF
FDVVLVDQPC IGNAADADVL LTSLSSTTKQ DGVLAVRTYD SQLDPMDYIQ RSSEWKVSGR
IRDGDFLLAH RQRIPAPLDS TIFVLMPDTE QIPPTFRVAL ERALSAVGVK LCPVDVEDIN
GLAGKMVISL LEFRHPWTSK WTSVAMAQFK MLLEARYILW VSPIPILSKD ASAASFGAST
GLLRTLRNEQ PGVTLPQVQY DPDDPNSETS LAQGILQVIQ LTLVPVPHRN HDMEYRLQHG
RLLVPRVVSE AVVDDKMQTL LHGPRPILAR LADDPRALRF HAGSPDGHGG QWVEDRQLVS
DVPDDHVEVQ LSLRSVVARG SRNFNAHESR LSVVEAVGVI RKLGFAGSTD LSVGDIVVLL
VPGAGTVDGM SNRIQVSSKA VAKLPAQLTL AQAVTVPLAY ILAYTSLFDI ARLGPNCRVL
LVGPVGPILR ALLSCALEIR GMQVYVATEE RAVVEELVAQ YAIAPEYVLS IHGGLDGRIA
DLTEGKGVTA VLSCLGGSSG RLAARCLGSG GHYVDLTGEM NLAALPKAVV SQGCTFTSVN
LNSMLQNQSE KVYSSFRRAV ATIGLHHQIQ PTSIFPISKW AEAESLARQT GISVAIDFTD
PGQVPVVPAL QEPVNLPPQQ TYLLAGGLGM IGLGFAKTLV DSGARHLVIL SRSGVLQPSQ
RIAVASLADQ GCHVEIIRCD ISQEADLQQV LSQVRSQNWQ LKGIIQCATV LKDAAFHTMT
FEDWASSTNP KILGTLNLHK VFVDVDLDFF ITLSSVSGLI GNIGQANYAA GNVFMDELMI
WRRAHGLPGH SIDIGLVPDA SGMSDMAETA EVRRSRYSHL EGTEITLREL QMLLRVIILG
DIPVPVQIIA GITDDLPREG ASSWQYDRKL DHRVRLGHSE PDNMPAQISE LLKSSPTIED
ASYVVNQALR EYLASAMATT ADTIDSDLPL SSLGVDSLKV TEVQNWVSRK MGAQLSSFDF
LGMQPLRVLS EKIAAQSAFV TVS
