HELD1_ASPFU
ID HELD1_ASPFU Reviewed; 478 AA.
AC Q4WR21;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Acyltransferase helD1 {ECO:0000303|PubMed:29158519};
DE EC=2.3.1.- {ECO:0000269|PubMed:29158519, ECO:0000305|PubMed:19415934};
DE AltName: Full=Helvolic acid biosynthesis cluster protein D1 {ECO:0000303|PubMed:29158519};
GN Name=helD1 {ECO:0000303|PubMed:29158519}; ORFNames=AFUA_4G14820;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP INDUCTION.
RX PubMed=17432932; DOI=10.1371/journal.ppat.0030050;
RA Perrin R.M., Fedorova N.D., Bok J.W., Cramer R.A., Wortman J.R., Kim H.S.,
RA Nierman W.C., Keller N.P.;
RT "Transcriptional regulation of chemical diversity in Aspergillus fumigatus
RT by LaeA.";
RL PLoS Pathog. 3:E50-E50(2007).
RN [3]
RP FUNCTION, AND PATHWAY.
RX PubMed=19415934; DOI=10.1021/ja8095976;
RA Mitsuguchi H., Seshime Y., Fujii I., Shibuya M., Ebizuka Y., Kushiro T.;
RT "Biosynthesis of steroidal antibiotic fusidanes: functional analysis of
RT oxidosqualene cyclase and subsequent tailoring enzymes from Aspergillus
RT fumigatus.";
RL J. Am. Chem. Soc. 131:6402-6411(2009).
RN [4]
RP FUNCTION.
RX PubMed=19216560; DOI=10.1021/ol802696a;
RA Lodeiro S., Xiong Q., Wilson W.K., Ivanova Y., Smith M.L., May G.S.,
RA Matsuda S.P.;
RT "Protostadienol biosynthesis and metabolism in the pathogenic fungus
RT Aspergillus fumigatus.";
RL Org. Lett. 11:1241-1244(2009).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=29158519; DOI=10.1038/s41467-017-01813-9;
RA Lv J.M., Hu D., Gao H., Kushiro T., Awakawa T., Chen G.D., Wang C.X.,
RA Abe I., Yao X.S.;
RT "Biosynthesis of helvolic acid and identification of an unusual C-4-
RT demethylation process distinct from sterol biosynthesis.";
RL Nat. Commun. 8:1644-1644(2017).
CC -!- FUNCTION: Acyltransferase; part of the gene cluster that mediates the
CC biosynthesis of helvolic acid, an antibacterial nortriterpenoid
CC (PubMed:19415934, PubMed:19216560, PubMed:29158519). Protostadienol
CC synthase helA cyclizes (3S)-oxidosqualene to (17Z)-protosta-17(20),24-
CC dien-3-beta-ol (protostadienol)(PubMed:19415934, PubMed:19216560,
CC PubMed:29158519). The synthesis of protostadienol is followed by
CC several steps of monooxygenation, dehydrogenation, and acyl transfer to
CC yield the final helvolic acid (PubMed:19216560). Following the
CC cyclization to the tetracyclic protostadienol by helA, cytochrome P450
CC monooxygenases helB1-mediated and helB2-mediated oxidation at C-4 and
CC C-16, acyltransferase helD2-dependent acetylation of 16-OH, oxidation
CC of C-21 by cytochrome P450 monooxygenase helB4, and short chain
CC dehydrogenase helC-dependent oxidative decarboxylation yield the
CC fusidane skeleton (PubMed:29158519). This intermediate is further
CC modified in three additional steps mediated by the cytochrome P450
CC monooxygenase helB3, the acyltransferase helD1, and the 3-ketosteroid
CC 1-dehydrogenase helE to give helvolic acid (PubMed:19415934,
CC PubMed:19216560, PubMed:29158519). Compared with the late stages in the
CC biosynthesis of helvolic acid, enzymes involved in the early stage
CC modifications act in a relatively strict order (PubMed:29158519). The
CC hydroxylation of C-16 by helB1 and subsequent acetylation by helD2
CC should occur before the helB3-mediated oxidation of C-21
CC (PubMed:29158519). C-4 demethylation in fusidane-type antibiotics
CC proceeds in an unusual manner though it is also achieved by oxidative
CC decarboxylation (PubMed:19415934, PubMed:29158519). The methyl group at
CC C-4 beta position is oxidized by helB1 and subsequently removed by the
CC short chain dehydrogenase helC (PubMed:19415934, PubMed:29158519).
CC {ECO:0000269|PubMed:19216560, ECO:0000269|PubMed:19415934,
CC ECO:0000269|PubMed:29158519}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:29158519,
CC ECO:0000305|PubMed:19415934}.
CC -!- INDUCTION: Expression is under the control of the secondary metabolism
CC regulator laeA (PubMed:17432932). {ECO:0000269|PubMed:17432932}.
CC -!- SIMILARITY: Belongs to the plant acyltransferase family. {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89313.1; -; Genomic_DNA.
DR RefSeq; XP_751351.1; XM_746258.1.
DR AlphaFoldDB; Q4WR21; -.
DR SMR; Q4WR21; -.
DR EnsemblFungi; EAL89313; EAL89313; AFUA_4G14820.
DR GeneID; 3508869; -.
DR KEGG; afm:AFUA_4G14820; -.
DR VEuPathDB; FungiDB:Afu4g14820; -.
DR eggNOG; ENOG502SMM1; Eukaryota.
DR HOGENOM; CLU_563912_0_0_1; -.
DR InParanoid; Q4WR21; -.
DR OMA; YENTQSE; -.
DR OrthoDB; 1130893at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0016747; F:acyltransferase activity, transferring groups other than amino-acyl groups; IBA:GO_Central.
DR GO; GO:1900812; P:helvolic acid biosynthetic process; IDA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; IGC:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.30.559.10; -; 2.
DR InterPro; IPR023213; CAT-like_dom_sf.
PE 1: Evidence at protein level;
KW Acyltransferase; Reference proteome; Transferase.
FT CHAIN 1..478
FT /note="Acyltransferase helD1"
FT /id="PRO_0000441951"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8W1W9"
FT ACT_SITE 415
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q8W1W9"
SQ SEQUENCE 478 AA; 53274 MW; 6D5ACF3033D29E16 CRC64;
MESIPLSPFD LQGSFSNIPY AFFYENTQSE NDFMPFDFLK GSLWASLQRF PILTGRLRAR
STGHIVVEVD AGNPNQPDIR ETLCDSVHWS QLKESSFAWD AWPAGVATVG PVATAAADGE
IKLLNIHVMR LAQNSGVILF INIPHYVVDG VGYFAFINHW AETMRMQQQQ QEQENEARSR
FSFDRGIIQR YLPTERAPLD PLTASIYGQR NLLVDWLAWL SPTTLGGLLS KTAAMARGEA
HLFRIPRASL DQVHKDVQPY IPASARLSDN DLLVALISKT YIQSQPQPKP PTGFLSWLRP
GQGQPESHCT VRIPCDVRRH LKVRERYTGN LLLGMMVRTP LAELARPTSS ETLAAAALNV
RQSIERVQPG LVAAYHDLIQ ANPTSHMRPL AFTATRTTTS LVTTSQVRFP MYEADFGSGK
PCFVCLTPVF AGSYTMAAIL PTPEGREGGV YVLLTSNVEA MQGIKKNQYW NGLVEIIW
