AUSA_PENBI
ID AUSA_PENBI Reviewed; 2475 AA.
AC A0A0F7U103; A0A0F7TZE3;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 33.
DE RecName: Full=Non-reducing polyketide synthase ausA {ECO:0000303|PubMed:29076725};
DE EC=2.3.1.- {ECO:0000305|PubMed:29076725};
DE AltName: Full=Austinoid biosynthesis clusters protein A {ECO:0000303|PubMed:29076725};
GN Name=ausA {ECO:0000303|PubMed:29076725}; ORFNames=PMG11_09856;
OS Penicillium brasilianum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=104259;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MG11;
RX PubMed=26337871; DOI=10.1128/genomea.00724-15;
RA Horn F., Linde J., Mattern D.J., Walther G., Guthke R., Brakhage A.A.,
RA Valiante V.;
RT "Draft genome sequence of the fungus Penicillium brasilianum MG11.";
RL Genome Announc. 3:0-0(2015).
RN [2]
RP FUNCTION.
RX PubMed=27602587; DOI=10.1021/jacs.6b08424;
RA Matsuda Y., Iwabuchi T., Fujimoto T., Awakawa T., Nakashima Y., Mori T.,
RA Zhang H., Hayashi F., Abe I.;
RT "Discovery of key dioxygenases that diverged the paraherquonin and
RT acetoxydehydroaustin pathways in Penicillium brasilianum.";
RL J. Am. Chem. Soc. 138:12671-12677(2016).
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 A
CC that mediates the biosynthesis of the fungal meroterpenoid
CC acetoxydehydroaustin (PubMed:29076725). The first step of the pathway
CC is the synthesis of 3,5-dimethylorsellinic acid by the polyketide
CC synthase ausA (By similarity). 3,5-dimethylorsellinic acid is then
CC prenylated by the polyprenyl transferase ausN (By similarity). Further
CC epoxidation by the FAD-dependent monooxygenase ausM and cyclization by
CC the probable terpene cyclase ausL lead to the formation of
CC protoaustinoid A (By similarity). Protoaustinoid A is then oxidized to
CC spiro-lactone preaustinoid A3 by the combined action of the FAD-binding
CC monooxygenases ausB and ausC, and the dioxygenase ausE (By similarity).
CC Acid-catalyzed keto-rearrangement and ring contraction of the
CC tetraketide portion of preaustinoid A3 by ausJ lead to the formation of
CC preaustinoid A4 (By similarity). The aldo-keto reductase ausK, with the
CC help of ausH, is involved in the next step by transforming preaustinoid
CC A4 into isoaustinone which is in turn hydroxylated by the P450
CC monooxygenase ausI to form austinolide (By similarity). The cytochrome
CC P450 monooxygenase ausG then modifies austinolide to austinol (By
CC similarity). Austinol is further acetylated to austin by the O-
CC acetyltransferase ausP, which spontaneously changes to dehydroaustin
CC (PubMed:29076725). The cytochrome P450 monooxygenase then converts
CC dehydroaustin is into 7-dehydrodehydroaustin (PubMed:29076725). The
CC hydroxylation catalyzed by ausR permits the second O-acetyltransferase
CC ausQ to add an additional acetyl group to the molecule, leading to the
CC formation of acetoxydehydroaustin (PubMed:29076725). Due to genetic
CC rearrangements of the clusters and the subsequent loss of some enzymes,
CC the end product of the Penicillium brasilianum austinoid biosynthesis
CC clusters is acetoxydehydroaustin (PubMed:29076725).
CC {ECO:0000250|UniProtKB:Q5ATJ7, ECO:0000269|PubMed:29076725}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 3 malonyl-CoA + 2 S-adenosyl-L-methionine = 3,5-
CC dimethylorsellinate + 3 CO2 + 4 CoA + 2 S-adenosyl-L-homocysteine;
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:0000305|PubMed:29076725}.
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 -!- 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CEJ61321.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CDHK01000010; CEJ61321.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CDHK01000010; CEJ61320.1; -; Genomic_DNA.
DR SMR; A0A0F7U103; -.
DR STRING; 104259.A0A0F7U103; -.
DR EnsemblFungi; CEJ61320; CEJ61320; PMG11_09856.
DR EnsemblFungi; CEJ61321; CEJ61321; PMG11_09856.
DR OrthoDB; 93381at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000042958; 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:0008236; F:serine-type peptidase activity; 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:0006508; P:proteolysis; 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; -; 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 Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR013094; AB_hydrolase_3.
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; IPR001375; Peptidase_S9.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF07859; Abhydrolase_3; 1.
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; PF00326; Peptidase_S9; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 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; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 3: Inferred from homology;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2475
FT /note="Non-reducing polyketide synthase ausA"
FT /id="PRO_0000453845"
FT DOMAIN 1626..1703
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 14..253
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 384..747
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 910..1212
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1282..1585
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1865..2098
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2127..2475
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 549
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 997
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 2250
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2412
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2444
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT MOD_RES 1663
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2475 AA; 269648 MW; E0907E4620A1F792 CRC64;
MGSLGDLPLN RISVLFGSKY SEIDRSALHI RRYLSTHRAA TWLEDAVEDL PSVWQDVTKV
WPAGEGIHGE AGLQQLSAFL RGEELPLNME DPMNYLLMPI TVLRHLVDFH EFKEAGSDCD
IKSMQGFCAG YLAAVAGCWE KDQSEFSKVV ATMVRTAIFI GAAVDLDELA TQRATSIAVR
WKTAEAYKPF AATLGRYPGA YIACITDESS VTVTVWEDQA AALVQELEGN GLLVKDTRLR
GRFHHADHLS AAQDILKLCQ QDTRFQLPNT CPARELPRSN ADGDLPTLKS VLSVVIQSIL
ISQADWNLTV SNTLNSLDSS DAKCILSIGA GQFLPRQARS QILNAIDSSR GDNLVNGDHD
NIAITNGTSF AASSVNGTAP VPTSIPIAVT GLACRYPQAD CVEELWKILE QGLCTVSRMP
ESRLKPDRLQ RKPDGPFWGN FISRPDAFDH RFFKISAREA ESMDPQQRLL LQVAYEAMES
AGYCGLRATN LPEDVGCYVG VGTEDYSENV GSRNATAFSA TGTLQAFNSG RVSHHFGWTG
PSVTVDTACS SAAVAIHLAC QALQTSDCSV AVAGGVNVMT DPRWSQNLAA ASFLSPTGAS
KAFDTNANGY CRGEGAGLVV LRPLEAALRD GDPIHAVITG TSVNQGANCS PITVPDSNSQ
RSLYMKALSL SGLKPEVVSY VEAHGTGTQV GDPIEFESIR KTFAVPSRTE RLYVGSIKDN
IGHTETSSGV AGLLKTILML QKGKIPKQAN FTQLNPKIIV NQEDQMSIPT SLIRWETQKR
VAMVTNYGAA GSNAAIVLKE PIPTPTALCS DEKERLLSAV PFFVAAQTEE SLREYCQALK
ARLLNGAHLE SIAVQDLAFN LARKQNRSME FSVSFTNSSS VTELRERLDD VISGRMNIVK
KTHTSNPVVL CFGGQTGNKA SISESLVASS ALIRLHLDEC ESACKALGLP SLFPAIFDSS
PNKDIVNLHC VLFSIQYATA KAWIDSGLEV DRMIGHSFGQ LTAVCVAGGL SLIDTMRLIS
TRAHLIRSEW TSEIGVMLSL KGEKNAVRDL LDSVPDSADL ACVNGADSFV AAGSEVAIHE
IEKNAAERGI KSQRLDNTHA FHSRLVDPIL PGLAKVASSL NYKPLRIPVE ACSESKEDWM
LPTWEKIVQH SRKPVYFHQA VHRTISRIQG PAIWLEAGTM SPIIGMVRRA VDTPSSARGH
VFCPMDLSGP QAESNLAKVT SSLWSNGVPV QFWPFHGSQR GYQWINLPPY QFAKTSHWIE
YDPTAFSYQM SKQEKPPIED LKLVQLLKNE GKVSLFRIND NDPMFRMCTA GHAVVEQNLC
PASLYFELVV RAAITTLPKG TDPTMYHLAD LNISAPLVLD MPGSVLLELT QRDSTPGQWT
FVLFTREDTL QSVTHATGTI SLSPGADNTG ISSRFSSLKR LLNPAHWDSI ATSPSSSGLK
RSTVYQAFRR AVTYAEYYRG VESVYALGHE ATGRVHLPSS PTKNSPCDPI LIDNFLQVAG
IHVNCLSETH DDEVFVCSSV GDVIIGESFV KRDPSVAAPW VVYSNYEQES KKKALCDVFV
VDEATGSLAL CVLAATFTSV SIQSLRRTLT RLTNKGVSPV PVDIAVAAEV TPAVPAASSI
TATRASSNGD DLRTVQAMLS ELLGIPTSEI PASASLADVG VDSLMNTEVL SEIKNRFQVV
ITKSELTAIE DVGALVQRIF PGRSTVHIEN HDQPAVGITA INGGSKPSSG GPVPASKVGD
DLSGFADKAG ELFTASRKSN EHSEATKFLG FCDTVFPQQM ELVTAYVVEA FKVLGVDLQS
LKAGQPIPSV DILPQHGQVM NQLYAVLEYS GLVDRSGTSI CRGHCEVNQD ATAVLHQKIL
NDHPQHTSEH KLLHTTGPRL ADCLTGAADP LSLLFQDAQA RALMQDVYSN APMFKSATMH
LAQYLKNLLR QVNSPRPIKI LEIGAGTGGT TDYLLKQLSS VAGLRFEYTF TDISPSLVTL
ARKRFKTFNF IHYQTLDIEK GPASEMLGQY DIIVSSNCIH ATRSLSTSCS NIQKLLRPHG
ILCLIELTRN LFWFDLVFGL LEGWWLFNDG RSHALAHESF WDQTLRSSGF NWVDWTDNQS
EESNILRLIV ASPTRPALSL EATTESSAIH EETVVYGRKD GLDLLADIHY PQILDSEGKN
RPVALLIHGG GHIMLSRKDV RPPQVKLLID MGFLPVSIDY RLCPEVSLLE GPMADACEAL
AWAQNTLPQL NLQRPDIRPD GNNVVAVGWS SGGHLAMTLA WTAPARGLRA PEAVLSFYCA
TDYTDPFWTK PNFPYQGDVS IEDVPTQSPF LGINDRAITS YNPAPRKRAL GGWMSPTDPR
SRIALHMNWT GQTLTVLFNG HKYKSLVAIA GGDDNVILPK PTLSEIQKAC PLSHVYAGQY
KTPTFIIHGT LDDLIPVEQS QRTHDQMLAN GVESELRVVA DAPHLFDMSP NLKNNKDACR
AVADGYEFLR SHVGL
