ID AUSV_ASPCI Reviewed; 2531 AA.
AC A0A0U5GK88;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 27-NOV-2024, entry version 45.
DE RecName: Full=Highly reducing polyketide synthase ausV {ECO:0000303|PubMed:28233494};
DE EC=2.3.1.- {ECO:0000269|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein V {ECO:0000303|PubMed:28233494};
GN Name=ausV {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14365;
OS Aspergillus calidoustus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=454130;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SF006504;
RX PubMed=26966204; DOI=10.1128/genomea.00102-16;
RA Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Scherlach K.,
RA Martin K., Brakhage A.A., Petzke L., Valiante V.;
RT "Draft genome sequences of fungus Aspergillus calidoustus.";
RL Genome Announc. 4:0-0(2016).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28233494; DOI=10.1021/acschembio.7b00003;
RA Valiante V., Mattern D.J., Schueffler A., Horn F., Walther G.,
RA Scherlach K., Petzke L., Dickhaut J., Guthke R., Hertweck C., Nett M.,
RA Thines E., Brakhage A.A.;
RT "Discovery of an Extended Austinoid Biosynthetic Pathway in Aspergillus
RT calidoustus.";
RL ACS Chem. Biol. 12:1227-1234(2017).
RN [3]
RP FUNCTION.
RX PubMed=29076725; DOI=10.1021/acschembio.7b00814;
RA Mattern D.J., Valiante V., Horn F., Petzke L., Brakhage A.A.;
RT "Rewiring of the austinoid biosynthetic pathway in filamentous fungi.";
RL ACS Chem. Biol. 12:2927-2933(2017).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of calidodehydroaustin, a fungal
CC meroterpenoid (PubMed:28233494, PubMed:29076725). The first step of the
CC pathway is the synthesis of 3,5-dimethylorsellinic acid by the
CC polyketide synthase ausA (PubMed:28233494). 3,5-dimethylorsellinic acid
CC is then prenylated by the polyprenyl transferase ausN
CC (PubMed:28233494). Further epoxidation by the FAD-dependent
CC monooxygenase ausM and cyclization by the probable terpene cyclase ausL
CC lead to the formation of protoaustinoid A (By similarity).
CC Protoaustinoid A is then oxidized to spiro-lactone preaustinoid A3 by
CC the combined action of the FAD-binding monooxygenases ausB and ausC,
CC and the dioxygenase ausE (By similarity). Acid-catalyzed keto-
CC rearrangement and ring contraction of the tetraketide portion of
CC preaustinoid A3 by ausJ lead to the formation of preaustinoid A4 (By
CC similarity). The aldo-keto reductase ausK, with the help of ausH, is
CC involved in the next step by transforming preaustinoid A4 into
CC isoaustinone which is in turn hydroxylated by the P450 monooxygenase
CC ausI to form austinolide (By similarity). The cytochrome P450
CC monooxygenase ausG modifies austinolide to austinol (By similarity).
CC Austinol is further acetylated to austin by the O-acetyltransferase
CC ausP, which spontaneously changes to dehydroaustin (PubMed:28233494).
CC The cytochrome P450 monooxygenase ausR then converts dehydroaustin is
CC into 7-dehydrodehydroaustin (PubMed:28233494). The hydroxylation
CC catalyzed by ausR permits the O-acetyltransferase ausQ to add an
CC additional acetyl group to the molecule, leading to the formation of
CC acetoxydehydroaustin (PubMed:28233494). The short chain dehydrogenase
CC ausT catalyzes the reduction of the double bond present between carbon
CC atoms 1 and 2 to convert 7-dehydrodehydroaustin into 1,2-dihydro-7-
CC hydroxydehydroaustin (PubMed:28233494). AusQ catalyzes not only an
CC acetylation reaction but also the addition of the PKS ausV diketide
CC product to 1,2-dihydro-7-hydroxydehydroaustin, forming
CC precalidodehydroaustin (PubMed:28233494). Finally, the iron/alpha-
CC ketoglutarate-dependent dioxygenase converts precalidodehydroaustin
CC into calidodehydroaustin (PubMed:28233494).
CC {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:28233494,
CC ECO:0000269|PubMed:29076725}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28233494}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000250|UniProtKB:Q5KTM9}.
CC -!- MISCELLANEOUS: In A.calidoustus, the austinoid gene cluster lies on a
CC contiguous DNA region, while clusters from E.nidulans and P.brasilianum
CC are split in their respective genomes. Genetic rearrangements provoked
CC variability among the clusters and E.nidulans produces the least number
CC of austionoid derivatives with the end products austinol and
CC dehydroaustinol, while P.brasilianum can produce until
CC acetoxydehydroaustin, and A.calidoustus produces the highest number of
CC identified derivatives. {ECO:0000305|PubMed:29076725}.
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DR EMBL; CDMC01000024; CEL11262.1; -; Genomic_DNA.
DR SMR; A0A0U5GK88; -.
DR STRING; 454130.A0A0U5GK88; -.
DR OMA; ITHESHD; -.
DR OrthoDB; 5396558at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
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:TreeGrafter.
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 CDD; cd05195; enoyl_red; 1.
DR CDD; cd00833; PKS; 1.
DR FunFam; 3.40.47.10:FF:000019; Polyketide synthase type I; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.90.180.10; Medium-chain alcohol dehydrogenases, catalytic domain; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR011032; GroES-like_sf.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775:SF29; ASPERFURANONE POLYKETIDE SYNTHASE AFOG-RELATED; 1.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
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; PF08242; Methyltransf_12; 1.
DR Pfam; PF21089; PKS_DH_N; 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; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 3.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2531
FT /note="Highly reducing polyketide synthase ausV"
FT /id="PRO_0000453870"
FT DOMAIN 7..432
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 939..1238
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2444..2521
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 554..882
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5KTM9, ECO:0000255"
FT REGION 939..1069
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 940..1236
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5KTM9, ECO:0000255"
FT REGION 1087..1238
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1414..1592
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5KTM9, ECO:0000255"
FT REGION 1832..2133
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5KTM9, ECO:0000255"
FT REGION 2156..2331
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5KTM9, ECO:0000255"
FT ACT_SITE 180
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 315
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 355
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 644
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 971
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1152
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT MOD_RES 2481
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2531 AA; 275891 MW; D0A9F5922ECBC3F3 CRC64;
MAGTDSSTPI AIIGLSGRFP GEASNPQKLW SVLMNKQSTR SEVPPDRFNV NAFYHPSGSR
AGTVNTRWGH FMTRDPAAFD APFFSVLPEE ARAMDPQSRM ALECAFEAFE NAGMTMDAVA
GTRTACYVAS FTHDYAELLA QDGESQPRYK FTGCGAGMLA NRISWFFDLQ APSVTVDTAC
SSSLVALHLG CQSIHTGDAD MVLVGGANVI LSPQMMASQS SLGFLSPDGR SKAFDEQADG
YARGEGVGFL LLKPLGAALA DGDAIRAVIR GTGVNQDGRT AGITVPSAQA QERLIRSVYD
RACLDPVETP FVEAHGTGTR KGDLAEASSL ASVFCHRRLP QNPLYIGSVK TNIGHLEAAA
GVAQVIKTVL ALENGIIPPN IWFTRPSTAL PLDRWRLKVP VEPVSWPEGE KRRASINSFG
YGGTNAHCVM ETLEEYSMGQ GAAKAGTLCQ EPRCNHEARP REEEAPMLIF WSSHDKGGIS
RLAAQYAQYL EAKVKSATDR SSLTRRLCMT LHSRRSVMPW KSYIVSHSAN SIVESFRNGA
AQPLRSSEPP AIVFVFTGQG AQWPGMGRQL IRYPEYLESL QLAGRFLQCL GLQVSVIDEI
KATPEQSSLA SPEVSQTLCT VLQVALVDLL ESFGINPTAV IGHSGGEIAA AYAKGAISRE
AAWTIAFHRG RLCSSLPDYA PSLQGGMLVA GLGREDCATY IGRLTEGVAV IACVNSPLSC
TVAGDLSALD QLEGLLSEAG CFHRRLRVSR AYHSPHMQVI AGECYKAISS ARPLADTEKS
LNTTMYSTVT RGVVECSDLG PDYWVSNMIE PVEFVGAVES VIRDLGNRTA PTVFVEIGPH
SALQGPLRQI LDAASSAERF PYTSLLVRGR DAHHTLLESM GSLIQHGCHL KLHEINQLST
EEGFLVNLPP YPWNHDERNR YWAESSVSRK RRFRQHARHD LCGIRVEDDL PGEATWRNIL
SPSENPWILD HRVQGTIVYP AAGMLTAVVE AVRESVRNVL EISYFELRDV KISRPIVFSS
EEDVVHTRLR LRQETGQCPG SFEFQHYSEK GDGWELNCSG SVLAGTPSDS PDAAHRTRYA
HCRAASYVET TPRQAYSQWA SVGLQFGRWF QNLTQLSKGP SSAIGTVRIP STTDCMPCGF
EQDMLVHPVV LDALVQLGLS TSKEEYEEPH DTMVPVAFSR VHISADIPQG PGTEMVGYSV
INDSASGVNV AASDTQWAQP WIILDGLELA TLSVRSGDAV GPTAARVPRK LAAATEWLPS
IIHTPGDIIQ RACNLPGESM QADRACELQW AALIWIQRIL RGCPLTDVSP SPPHLRRLHH
GMTRLYNSAI QGDSFPEDSR LKMLLSSPRK VQDEALQQVA NSSIDGEILD HHCRMLDRIL
RGNMHSIEAL LEESRLHRWY AEGITWRANH DKVSSYLRLH ARNNAQAQIL EIGGGTGGLT
LSALRAMTLS DGSALFDSYC FTDISGGFFE KARKKFAAWA HCMSFVTLNI EHDLERQGFG
EAQFDLILAD NVLHATKSIR HTLSAVRKLL KPTGRLVLSE ITRNMPHITM TVGALEGWWL
GVEDGRVWEP TLSVEQWDGA LRDTGFSGVD ISLHDRPKGD HIMTGMVATA RQLGLTPPPT
PAVIIIHMHN LTPRVRTFVT GCITQLRALG MDVAVESLGS SSAHDNLHDK TVVLLLDADP
EQRDLATINE TEWTALKHTL LSCADAVWIT RGANADGWNP WASMAQGLVR SLRAENPATA
ITMVDIACEQ DLDSATTISS ITRLALAGRR AKITHESHDW EYCIRGREIL IPRVMTEDGV
NGAVFKSVKS ETEQIPFGQP GTSVALTTIE PLRFVQDPAY WLEPLGKDEA EVATRATHLV
SSQGQNNSSH GLVTVCGTVT RLGTACHSEL SVGDRVMTIQ RGAIRNLYRC PLTLCHRIPE
KLGDFGVAVR VLWAYTTAFY CLVHKASLKA GEAVLIDCAS NTLQESLIRL AQHARAEVFL
LVSSEARKNQ LASTFLVPPD HILSTGGEGL QGLDMGRRFD LILLDAAPTN LLQQYLAPGA
RLVLVQHQGR TQHSSFHGSN GSVDRHESWF LDSKGTRLRL PIPGDARMYT IAPDTLSHED
RTIVAQILRH VTELVRSQEI HADSGGAKPG CSRSEESLHI TNCVEGAPNQ LVVEAHGRAL
VPDFHNKVIK SRPTAHLLPN ATYIIAGGSG GLGASLARWM CHRGARHIVI LSRQADTRPG
VAKLIEDLAV NGVKVAAVPC DITDSQQDSV FHNMSFGAWN RAIHPKVMGS WNLHTHCPSE
VDFFILLSSF VGTVGLRGQA NYAAGNSFQD ALAHHRRSRG QAGVSLSLGF IDGAGFIAQS
SGRVAENVSK FNFLHIQQSE FLQLVELAVT SPDRLPAQVI TGCGTGGMVA AREGDPGDVY
WLRDPRFQLL AQVDLHHFQR MNSEPAAEGF SLGALLAAAE TVGAAATAVL DALCRKLATA
ASIEAGDIDT SRQLSSYGVD SLLAVDLRAY LATEARLDIS VFELMRSRPM RELARDLALR
SKYFRSSHVA T
//
