ALDH1_ARTAN
ID ALDH1_ARTAN Reviewed; 499 AA.
AC C5I9X1;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Aldehyde dehydrogenase 1 {ECO:0000303|Ref.1};
DE EC=1.2.1.- {ECO:0000269|Ref.1};
DE AltName: Full=Artemisinic aldehyde oxidase {ECO:0000305|Ref.1};
DE Short=Artemisinate synthase {ECO:0000305|Ref.1};
DE AltName: Full=Dihydroartemisinic aldehyde oxidase {ECO:0000305|Ref.1};
GN Name=ALDH1 {ECO:0000303|Ref.1};
GN ORFNames=CTI12_AA036970 {ECO:0000312|EMBL:PWA96689.1};
OS Artemisia annua (Sweet wormwood).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC asterids; campanulids; Asterales; Asteraceae; Asteroideae; Anthemideae;
OC Artemisiinae; Artemisia.
OX NCBI_TaxID=35608;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX DOI=10.1139/B09-032;
RA Teoh K.H., Polichuk D.R., Reed D.W., Covello P.S.;
RT "Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin
RT biosynthesis in Artemisia annua.";
RL Botany 87:635-642(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Huhao1; TISSUE=Leaf;
RX PubMed=29703587; DOI=10.1016/j.molp.2018.03.015;
RA Shen Q., Zhang L., Liao Z., Wang S., Yan T., Shi P., Liu M., Fu X., Pan Q.,
RA Wang Y., Lv Z., Lu X., Zhang F., Jiang W., Ma Y., Chen M., Hao X., Li L.,
RA Tang Y., Lv G., Zhou Y., Sun X., Brodelius P.E., Rose J.K.C., Tang K.;
RT "The genome of Artemisia annua provides insight into the evolution of
RT Asteraceae family and artemisinin biosynthesis.";
RL Mol. Plant 11:776-788(2018).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=22195571; DOI=10.1016/j.plantsci.2011.10.019;
RA Olofsson L., Lundgren A., Brodelius P.E.;
RT "Trichome isolation with and without fixation using laser microdissection
RT and pressure catapulting followed by RNA amplification: expression of genes
RT of terpene metabolism in apical and sub-apical trichome cells of Artemisia
RT annua L.";
RL Plant Sci. 183:9-13(2012).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=23575629; DOI=10.1038/nature12051;
RA Paddon C.J., Westfall P.J., Pitera D.J., Benjamin K., Fisher K., McPhee D.,
RA Leavell M.D., Tai A., Main A., Eng D., Polichuk D.R., Teoh K.H., Reed D.W.,
RA Treynor T., Lenihan J., Fleck M., Bajad S., Dang G., Diola D., Dorin G.,
RA Ellens K.W., Fickes S., Galazzo J., Gaucher S.P., Geistlinger T., Henry R.,
RA Hepp M., Horning T., Iqbal T., Jiang H., Kizer L., Lieu B., Melis D.,
RA Moss N., Regentin R., Secrest S., Tsuruta H., Vazquez R., Westblade L.F.,
RA Xu L., Yu M., Zhang Y., Zhao L., Lievense J., Covello P.S., Keasling J.D.,
RA Reiling K.K., Renninger N.S., Newman J.D.;
RT "High-level semi-synthetic production of the potent antimalarial
RT artemisinin.";
RL Nature 496:528-532(2013).
RN [5]
RP REVIEW ON ARTEMISININ ANTIMALARIAL PROPERTIES.
RX PubMed=27488942; DOI=10.1002/anie.201601967;
RA Tu Y.;
RT "Artemisinin-A Gift from Traditional Chinese Medicine to the World (Nobel
RT Lecture).";
RL Angew. Chem. Int. Ed. 55:10210-10226(2016).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=30851440; DOI=10.1016/j.molp.2019.02.011;
RA Judd R., Bagley M.C., Li M., Zhu Y., Lei C., Yuzuak S., Ekeloef M., Pu G.,
RA Zhao X., Muddiman D.C., Xie D.-Y.;
RT "Artemisinin biosynthesis in non-glandular trichome cells of Artemisia
RT annua.";
RL Mol. Plant 12:704-714(2019).
RN [7]
RP PATHWAY, AND REVIEW.
RX PubMed=30468448; DOI=10.1039/c8np00077h;
RA Liu Y., Jing S.-X., Luo S.-H., Li S.-H.;
RT "Non-volatile natural products in plant glandular trichomes: chemistry,
RT biological activities and biosynthesis.";
RL Nat. Prod. Rep. 36:626-665(2019).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=32514287; DOI=10.1186/s13020-020-00336-8;
RA Uzun T., Toptas O.;
RT "Artesunate: could be an alternative drug to chloroquine in COVID-19
RT treatment?";
RL Chin. Med. J. 15:54-54(2020).
RN [9]
RP BIOTECHNOLOGY, AND REVIEW.
RX PubMed=32405226; DOI=10.1016/j.phrs.2020.104901;
RA Cheong D.H.J., Tan D.W.S., Wong F.W.S., Tran T.;
RT "Anti-malarial drug, artemisinin and its derivatives for the treatment of
RT respiratory diseases.";
RL Pharmacol. Res. 158:104901-104901(2020).
CC -!- FUNCTION: Involved in the biosynthesis of the antimalarial endoperoxide
CC artemisinin (Ref.1, PubMed:27488942). Catalyzes the NAD(P)-dependent
CC oxidation of artemisinin precursors, artemisinic and dihydroartemisinic
CC aldehydes, thus producing artemisinic and dihydroartemisinic acids,
CC respectively (Ref.1). Can use both NAD and NADP as proton donors
CC (Ref.1). {ECO:0000269|Ref.1, ECO:0000303|PubMed:27488942}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(+)-artemisinic aldehyde + H2O + NADP(+) = (+)-artemisinate +
CC 2 H(+) + NADPH; Xref=Rhea:RHEA:60680, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:64688, ChEBI:CHEBI:64782; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60681;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R)-dihydroartemisinic aldehyde + H2O + NADP(+) = (11R)-
CC dihydroartemisinate + 2 H(+) + NADPH; Xref=Rhea:RHEA:60684,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:64691, ChEBI:CHEBI:143905;
CC Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60685;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(11R)-dihydroartemisinic aldehyde + H2O + NAD(+) = (11R)-
CC dihydroartemisinate + 2 H(+) + NADH; Xref=Rhea:RHEA:60688,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:64691, ChEBI:CHEBI:143905;
CC Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60689;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NADP(+) + octanal = 2 H(+) + NADPH + octanoate;
CC Xref=Rhea:RHEA:59904, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17935, ChEBI:CHEBI:25646, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59905;
CC Evidence={ECO:0000269|Ref.1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(E)-non-2-enal + H2O + NADP(+) = (E)-non-2-enoate + 2 H(+) +
CC NADPH; Xref=Rhea:RHEA:60692, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:142592,
CC ChEBI:CHEBI:143908; Evidence={ECO:0000269|Ref.1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60693;
CC Evidence={ECO:0000269|Ref.1};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.58 uM for artemisinic aldehyde (in the presence of NADP, at pH
CC 8.5 and 30 degrees Celsius) {ECO:0000269|Ref.1};
CC KM=8.79 uM for dihydroartemisinic aldehyde (in the presence of NADP,
CC at pH 8.5 and 30 degrees Celsius) {ECO:0000269|Ref.1};
CC Vmax=11.1 nmol/min/mg enzyme with artemisinic aldehyde as substrate
CC (in the presence of NADP, at pH 8.5 and 30 degrees Celsius)
CC {ECO:0000269|Ref.1};
CC Vmax=17.3 nmol/min/mg enzyme with 2-nonenal as substrate (in the
CC presence of NADP, at pH 8.5 and 30 degrees Celsius)
CC {ECO:0000269|Ref.1};
CC Vmax=11.6 nmol/min/mg enzyme with octanal as substrate (in the
CC presence of NADP, at pH 8.5 and 30 degrees Celsius)
CC {ECO:0000269|Ref.1};
CC Vmax=0.05 nmol/min/mg enzyme with sinapaldehyde as substrate (in the
CC presence of NADP, at pH 8.5 and 30 degrees Celsius)
CC {ECO:0000269|Ref.1};
CC Vmax=0.02 nmol/min/mg enzyme with 2-phenylpropanal as substrate (in
CC the presence of NADP, at pH 8.5 and 30 degrees Celsius)
CC {ECO:0000269|Ref.1};
CC Vmax=72 nmol/min/mg enzyme with dihydroartemisinic aldehyde as
CC substrate (in the presence of NAD) {ECO:0000269|Ref.1};
CC Vmax=75 nmol/min/mg enzyme with dihydroartemisinic aldehyde as
CC substrate (in the presence of NADP) {ECO:0000269|Ref.1};
CC Note=kcat is 1.53 sec(-1) with artemisinic aldehyde as substrate (in
CC the presence of NADP, at pH 8.5 and 30 degrees Celsius) (Ref.1). kcat
CC is 7.74 sec(-1) with dihydroartemisinic aldehyde as substrate (in the
CC presence of NADP, at pH 8.5 and 30 degrees Celsius) (Ref.1).
CC {ECO:0000269|Ref.1};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|Ref.1};
CC -!- PATHWAY: Sesquiterpene biosynthesis. {ECO:0000303|PubMed:30468448}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000250|UniProtKB:P51977}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P20000}.
CC -!- TISSUE SPECIFICITY: Expressed both in apical and sub-apical cells of
CC glandular secretory trichomes (PubMed:22195571, Ref.1). Also present in
CC flower buds and, at low levels, in leaves (Ref.1). Also present in non-
CC glandular trichome cells (PubMed:30851440).
CC {ECO:0000269|PubMed:22195571, ECO:0000269|PubMed:30851440,
CC ECO:0000269|Ref.1}.
CC -!- BIOTECHNOLOGY: Artemisinin and derivatives (e.g. artesunate), are
CC antimalarial drugs due to their endoperoxidase properties; they also
CC display multiple pharmacological actions against inflammation,viral
CC infections, and cell and tumor proliferation (PubMed:32514287,
CC PubMed:32405226). Artesunate may be a promising treatment for COVID-19
CC mediated by the severe acute respiratory syndrome coronavirus 2 (2019-
CC nCoV) (SARS-CoV-2) because of its anti-inflammatory activity, NF-kappaB
CC (nuclear factor kappa B)-coronavirus effect and chloroquine-like
CC endocytosis inhibition mechanism (PubMed:32514287, PubMed:32405226).
CC {ECO:0000303|PubMed:32405226, ECO:0000303|PubMed:32514287}.
CC -!- BIOTECHNOLOGY: Yeast (S.cerevisiae) has been engineered to produce
CC artemisinic-acid, a precursor of the antimalarial artemisinin compound,
CC by expressing AMS1/ADS, CYP71AV1, ADH1 and ALDH1 in conjunction with
CC CYB5 and CPR1. {ECO:0000269|PubMed:23575629}.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; FJ809784; ACR61719.1; -; mRNA.
DR EMBL; PKPP01000165; PWA96689.1; -; Genomic_DNA.
DR AlphaFoldDB; C5I9X1; -.
DR SMR; C5I9X1; -.
DR STRING; 35608.C5I9X1; -.
DR BRENDA; 1.14.14.114; 7150.
DR Proteomes; UP000245207; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016620; F:oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS_CYS.
DR InterPro; IPR029510; Ald_DH_CS_GLU.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..499
FT /note="Aldehyde dehydrogenase 1"
FT /id="PRO_0000447846"
FT ACT_SITE 266
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10007"
FT ACT_SITE 300
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10008"
FT BINDING 164..166
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 190..193
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 223
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 243..248
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT BINDING 397..399
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P20000"
FT SITE 167
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:P20000"
SQ SEQUENCE 499 AA; 53800 MW; DED56F85E98A5A20 CRC64;
MSSGANGSSK SASHKIKFTK LFINGEFVDS ISGNTFDTIN PATEEVLATV AEGRKEDIDL
AVKAAREAFD NGPWPRMSGE ARRKIMLKFA DLIDENADEL TTLEVIDGGK LFGPVRHFEV
PVSSDTFRYF AGAADKIRGA TLKMSSNIQA YTLREPIGVV GHIIPWNGPA FMFATKVAPA
LAAGCTMVIK PAEHTPLTVL FLAHLSKLAG VPDGVINVVN GFGKTAGAAV SSHMDIDMVT
FTGSTEVGRT VMQAAALSNL KPVSLELGGK SPLIVFDDAD VDKAAEFAIL GNFTNKGEMC
VAGSRVFVQE GIHDVFVKKL EGAVKAWATR DPFDLATRHG PQNNKQQYDK VLSCINHGKK
EGATLVTGGK PFGKKGYYIE PTLFTNVTDD MTIAKEEIFG PVISVLKFKT VEEVIKRANA
TKYGLASGVF TKNIDVVNTV SRSIRAGAVW VNCYLALDRD APHGGYKMSG FGREQGLEAL
EHYLQIKTVA TPIYDSPWL
