ID AUSA_ASPCI Reviewed; 2462 AA.
AC A0A0U5GFS8;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 27-NOV-2024, entry version 47.
DE RecName: Full=Non-reducing polyketide synthase ausA {ECO:0000303|PubMed:28233494};
DE EC=2.3.1.- {ECO:0000269|PubMed:28233494};
DE AltName: Full=Austinoid biosynthesis cluster protein A {ECO:0000303|PubMed:28233494};
GN Name=ausA {ECO:0000303|PubMed:28233494}; ORFNames=ASPCAL14369;
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, DISRUPTION PHENOTYPE, 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: Non-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 -!- CATALYTIC ACTIVITY:
CC Reaction=3 malonyl-CoA + acetyl-CoA + 2 S-adenosyl-L-methionine = 3,5-
CC dimethylorsellinate + 2 S-adenosyl-L-homocysteine + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:49628, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:131856;
CC Evidence={ECO:0000250|UniProtKB:Q5ATJ7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49629;
CC Evidence={ECO:0000250|UniProtKB:Q5ATJ7};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28233494}.
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:0000250|UniProtKB:Q5ATJ7}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-terminus of the protein.
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC -!- DISRUPTION PHENOTYPE: Impairs the biosynthesis of calidodehydroaustin.
CC {ECO:0000269|PubMed:28233494}.
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; CEL11266.1; -; Genomic_DNA.
DR SMR; A0A0U5GFS8; -.
DR STRING; 454130.A0A0U5GFS8; -.
DR ESTHER; aspci-ausa; Hormone-sensitive_lipase_like.
DR OMA; KDNIGHT; -.
DR OrthoDB; 5396558at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000054771; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0008168; F:methyltransferase 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: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; cd02440; AdoMet_MTases; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 2.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR029058; AB_hydrolase_fold.
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; IPR049492; BD-FAE-like_dom.
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; IPR020807; PKS_DH.
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; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF21; NON-REDUCING POLYKETIDE SYNTHASE AUSA-RELATED; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF20434; BD-FAE; 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 SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SMART; SM01294; PKS_PP_betabranch; 1.
DR SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
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; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2462
FT /note="Non-reducing polyketide synthase ausA"
FT /id="PRO_0000453844"
FT DOMAIN 385..801
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 1274..1581
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1613..1690
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 16..253
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 904..1208
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1274..1403
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1277..1580
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1431..1581
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1850..2083
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2112..2462
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 550
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 685
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 724
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 991
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1307
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1489
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 2235
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2398
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2430
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT MOD_RES 1650
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2462 AA; 267853 MW; FA1238E38219D429 CRC64;
MGPQTPSSEP PRPVTVFFGP VYPELTQSSS RIRQYLADKA SAGWLDDTLQ GLPSTWQDIM
RQWPALKKIP GESLLRQLTQ YLCRESSCPV GDTLNLLLVP VTVLRHIVEF QQLKDEKKHL
EIRDVQGFCV GVLAAITASW EHDDAEFPKV VSTVLRVAVC IGALVDLDEV NGSSSKSMAV
RWKTKCEYRH LGQVLERYKG YIACMIKTNG ATVTVPTANY LSLAEELESH GISVKNLPLR
GRFHTADHIP AMKQLLALCA RDARFQLPIK KNLPLLPRSN VDGTRLPSNV LMAAAVESIL
AKQANWMLTV AEALNSEGPP DEKHAVVIGA GQIIPQRSLL ASVEHIGDQM APTDTSLHRP
SPTIDIRPTA QCNGTSPETS TQAVSAPIAV TGFACRYPQA DSVEALWTLL ERGQCTVSSM
PNHRLKADSL QRQPRGPFWG NYLESPESFD HRFFGVSARE AESMDPQQRL LLQVAYEAIE
SATYCGLRAT KLPDDVGCYI GVGSDDYSQN VGSRDATAFS ATGTLQAFNS GRISHFFGWS
GPSITVDTAC SSAAVAIHLA CRALQANDCS IAVAGGVNVM TDPRWSQNLA AASFLSPTGA
SKAFDAAADG YCRGEGAGLL VLRPLDAALR DGDPIHAVIT GTCVNQGANC SPITVPDSNS
QRSLYMKALA QSGLHPDAVC YVEAHGTGTQ VGDPIEYESI RCTFGGPQRT ETVYIGSIKD
NIGHTETSSG AAGMVKTILM IQKRRIPKQA NFSCLNPRIV THERDQIAIP TQSLEWKAAK
RVALVTNYGA AGSNAVIVVK EPIKPGVDRS TWPARVPFII TAKTEESLRE YCRELQHTLL
AQQQGSGSAT HHLAYNLAAK QNRCLEYQLS FSCEPAEVAT RLQDIAAGRS KPTRCTAPSP
PVVLCFGGQT GDTASISPTL VENCDILRSH LTQCDEVCHA LGLPGLFPTI FSPEPRTDLV
SLHCILFSIQ YASAKAWLDC GLVVDRMIGH SFGQLTAICV AGGLSLIDGL RLVSKRAALI
QEKWGPERGV MLSLKVTKTQ VQELLCAASG TVDVACFNGP QSFVLAGNEK SIAQVETLCV
QRGLEHHKKR LRNTHAFHSR LVEPLLPELS QVADTLDYSP LRIPVEACSE EPDHWARLTA
SKVVRHSREP VYFHPAVQRT LRHIPGPCVW LEAGSASPIV GMVRRVVKAS GPGGEHTYLP
IDLQESTAEC NLADVTKVLW SKGVPVQFWA FHGSPAGYKW INLPPYQFSK TRHWIDYDPY
AFHPTGALSE EEKHDDGLLQ LVERDANGCL FRINNQDPAY RMCTEGHAVV DQNLCPASLY
VEIVVRGAMT LSANGQAAAM AHIEALSISA PLVVDMPGSV CLSVTQIANN NDGGWMFSLF
SQDGDRTPIT HATGKVLLDP QAAGSAASAR FHSLKRLLDP GQFDSIPKSP SSNGLKRATV
YQAFRRAVNY ADYYRGVEEV YAVGHRAAGR VLLPSSPTRM AACDPILMDN FLQVAGIHVN
CLSETDEDEV FVCSSVGEVS LGSRYLNRDA ATPQAWTVYS TYERESGKRV TCDVFALDED
RMLAVTIMSA TFTSVSIQSL KRTLSRLNGH SSSLGQHEPQ LQEKLAPAAH ITVSDDHHLR
AVQSMLGDLL GVSPGELPGN APLAEIGVDS LMSTEVLAEV DKRFGVNITN TELADIADVR
GLAHRISPSS SVVHVETSKE SSVANDISVG GQQPIIESPP VTHQEDSPRF ADRAITAFAA
TRGSTKYIDL TQFSAFCTSV YPQQMRLVTA YVAEAFQALG ANLESMLPGQ SIPSLAILPQ
HNQVLGQLIG VLEYAGLVEQ KSTGLFRTGK PVDVGPSAVL HQTILGDYPQ HASEHKLLRT
TGARLAECLT GTADPLSLLF QDAQARALMQ DVYSNAPMFK AATMQLAQYL QDLLLDSGCD
REIEILEIGA GTGGTTAFLV SQLAAMPGVK FKYTFTDLSS SLVTLARKRF GSYSFMRYST
LDIEKMPRDE LLGKYDIILS SNCIHATRSL AASCMHIRKM LRPHGLLCLI ELTRNLPWFD
LVFGLLGGWW LFNDGRSHAL ANESLWDTRL REAGFNWVDW TDNPLEESDI LRLIVASPTM
ASPPLPVKQP ITPARVETVR YGERAGVQLM ADIYYPHTVD AKGTKRPIAL LIHGGGHIML
SRKDIRPYQV DLLLDAGFLP VSIDYRLCPE VSLLEGPMPD VRDALAWARA DLPRQSLSRT
DIQPDGDRVV AVGWSTGGHL AMTLSWTAPE HGILPPQAIL AFYSPTDYTD PFWTTPNFPY
AGAVSEEDTK LTRPLDALRD SPITAYNPPA NKHALGGWMA PSDPRSQIAL YMNWTGQALP
VLFNGCNYKK LAAAKGPTTS EVILPAPPLA DVQRACPLSQ IVAGRYKTPT FLIHGGLDDL
IPVQQAERTQ DAMRAAGVES TLRVVQGGLH LFDLGIDISA VDEDGPRAVR EGYEFLRQHV
AV
//
