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Biotin synthase (EC

 BIOB_ECOLI              Reviewed;         346 AA.
P12996; Q2MBJ4;
01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
01-NOV-1997, sequence version 2.
13-FEB-2019, entry version 181.
RecName: Full=Biotin synthase;
EC= {ECO:0000269|PubMed:11862544, ECO:0000269|PubMed:17014080, ECO:0000269|PubMed:8142361};
Name=bioB; OrderedLocusNames=b0775, JW0758;
Escherichia coli (strain K12).
Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
Enterobacteriaceae; Escherichia.
Otsuka A.J., Buoncristiani M.R., Howard P.K., Flamm J., Johnson O.,
Yamamoto R., Uchida K., Cook C., Ruppert J., Matsuzaki J.;
"The Escherichia coli biotin biosynthetic enzyme sequences predicted
from the nucleotide sequence of the bio operon.";
J. Biol. Chem. 263:19577-19585(1988).
Pearson B.M., McKee R.A.;
"Genetic material for expression of biotin synthetase enzymes.";
Patent number GB2216530, 11-OCT-1989.
STRAIN=K12 / MG1655 / ATCC 47076;
PubMed=9278503; DOI=10.1126/science.277.5331.1453;
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J.,
Mau B., Shao Y.;
"The complete genome sequence of Escherichia coli K-12.";
Science 277:1453-1462(1997).
STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
PubMed=16738553; DOI=10.1038/msb4100049;
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
"Highly accurate genome sequences of Escherichia coli K-12 strains
MG1655 and W3110.";
Mol. Syst. Biol. 2:E1-E5(2006).
PubMed=8142361; DOI=10.1021/bi00178a020;
Sanyal I., Cohen G., Flint D.H.;
"Biotin synthase: purification, characterization as a [2Fe-2S] cluster
protein, and in vitro activity of the Escherichia coli bioB gene
Biochemistry 33:3625-3631(1994).
PubMed=9298644; DOI=10.1002/elps.1150180805;
VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R.,
Neidhardt F.C.;
"Escherichia coli proteome analysis using the gene-protein database.";
Electrophoresis 18:1243-1251(1997).
PubMed=11686925; DOI=10.1093/oxfordjournals.jbchem.a003028;
Farh L., Hwang S.-Y., Steinrauf L., Chiang H.-J., Shiuan D.;
"Structure-function studies of Escherichia coli biotin synthase via a
chemical modification and site-directed mutagenesis approach.";
J. Biochem. 130:627-635(2001).
PubMed=12440894; DOI=10.1021/ja0283044;
Cosper M.M., Jameson G.N.L., Davydov R., Eidsness M.K., Hoffman B.M.,
Huynh B.H., Johnson M.K.;
"The [4Fe-4S]2+ cluster in reconstituted biotin synthase binds S-
J. Am. Chem. Soc. 124:14006-14007(2002).
PubMed=11834738; DOI=10.1074/jbc.M111324200;
Ollagnier-de Choudens S., Sanakis Y., Hewitson K.S., Roach P.,
Muenck E., Fontecave M.;
"Reductive cleavage of S-adenosylmethionine by biotin synthase from
Escherichia coli.";
J. Biol. Chem. 277:13449-13454(2002).
PubMed=11862544; DOI=10.1007/s007750100268;
Hewitson K.S., Ollagnier-de Choudens S., Sanakis Y., Shaw N.M.,
Baldwin J.E., Muenck E., Roach P.L., Fontecave M.;
"The iron-sulfur center of biotin synthase: site-directed mutants.";
J. Biol. Inorg. Chem. 7:83-93(2002).
PubMed=12824504; DOI=10.1110/ps.0302203;
Cosper M.M., Cosper N.J., Hong W., Shokes J.E., Broderick W.E.,
Broderick J.B., Johnson M.K., Scott R.A.;
"Structural studies of the interaction of S-adenosylmethionine with
the [4Fe-4S] clusters in biotin synthase and pyruvate formate-lyase
activating enzyme.";
Protein Sci. 12:1573-1577(2003).
PubMed=19245793; DOI=10.1016/j.bbrc.2009.02.089;
Lotierzo M., Bui B.T., Leech H.K., Warren M.J., Marquet A.,
Rigby S.E.;
"Iron-sulfur cluster dynamics in biotin synthase: a new [2Fe-2S](1+)
Biochem. Biophys. Res. Commun. 381:487-490(2009).
PubMed=17014080; DOI=10.1021/bi060662m;
Lotierzo M., Raux E., Tse Sum Bui B., Goasdoue N., Libot F.,
Florentin D., Warren M.J., Marquet A.;
"Biotin synthase mechanism: mutagenesis of the YNHNLD conserved
Biochemistry 45:12274-12281(2006).
PubMed=14704425; DOI=10.1126/science.1088493;
Berkovitch F., Nicolet Y., Wan J.T., Jarrett J.T., Drennan C.L.;
"Crystal structure of biotin synthase, an S-adenosylmethionine-
dependent radical enzyme.";
Science 303:76-79(2004).
-!- FUNCTION: Catalyzes the conversion of dethiobiotin (DTB) to biotin
by the insertion of a sulfur atom into dethiobiotin via a radical-
based mechanism. {ECO:0000269|PubMed:8142361}.
Reaction=[sulfur carrier]-SH + dethiobiotin + 2 reduced [2Fe-2S]-
[ferredoxin] + 2 S-adenosyl-L-methionine = 2 5'-deoxyadenosine +
[sulfur carrier]-H + biotin + 2 L-methionine + 2 oxidized [2Fe-
2S]-[ferredoxin]; Xref=Rhea:RHEA:22060, Rhea:RHEA-COMP:10000,
Rhea:RHEA-COMP:10001, Rhea:RHEA-COMP:14737, Rhea:RHEA-
COMP:14739, ChEBI:CHEBI:17319, ChEBI:CHEBI:29917,
ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:57586,
ChEBI:CHEBI:57844, ChEBI:CHEBI:57861, ChEBI:CHEBI:59789,
ChEBI:CHEBI:64428; EC=;
ECO:0000269|PubMed:17014080, ECO:0000269|PubMed:8142361};
Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
cysteines and an exchangeable S-adenosyl-L-methionine.
Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:49601;
Note=Binds 1 [2Fe-2S] cluster. The cluster is coordinated with 3
cysteines and 1 arginine. {ECO:0000269|PubMed:8142361};
Kinetic parameters:
KM=2 uM for dethiobiotin {ECO:0000269|PubMed:8142361};
-!- PATHWAY: Cofactor biosynthesis; biotin biosynthesis; biotin from
7,8-diaminononanoate: step 2/2.
-!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:8142361}.
Q47147:yafJ; NbExp=4; IntAct=EBI-557917, EBI-1114805;
-!- SIMILARITY: Belongs to the radical SAM superfamily. Biotin
synthase family. {ECO:0000305}.
Copyrighted by the UniProt Consortium, see
Distributed under the Creative Commons Attribution (CC BY 4.0) License
EMBL; J04423; AAA23515.1; -; Genomic_DNA.
EMBL; A11530; CAA00965.1; -; Unassigned_DNA.
EMBL; U00096; AAC73862.1; -; Genomic_DNA.
EMBL; AP009048; BAE76362.1; -; Genomic_DNA.
RefSeq; NP_415296.1; NC_000913.3.
RefSeq; WP_000951213.1; NZ_LN832404.1.
PDB; 1R30; X-ray; 3.40 A; A/B=2-346.
PDBsum; 1R30; -.
ProteinModelPortal; P12996; -.
SMR; P12996; -.
BioGrid; 4259949; 37.
DIP; DIP-9220N; -.
IntAct; P12996; 17.
STRING; 316385.ECDH10B_0843; -.
DrugBank; DB03775; D-Dethiobiotin.
DrugBank; DB03754; Tris.
PaxDb; P12996; -.
PRIDE; P12996; -.
EnsemblBacteria; AAC73862; AAC73862; b0775.
EnsemblBacteria; BAE76362; BAE76362; BAE76362.
GeneID; 945370; -.
KEGG; ecj:JW0758; -.
KEGG; eco:b0775; -.
PATRIC; fig|1411691.4.peg.1503; -.
EchoBASE; EB0116; -.
EcoGene; EG10118; bioB.
eggNOG; ENOG4105CZF; Bacteria.
eggNOG; COG0502; LUCA.
HOGENOM; HOG000239957; -.
InParanoid; P12996; -.
KO; K01012; -.
PhylomeDB; P12996; -.
BioCyc; ECOL316407:JW0758-MONOMER; -.
BRENDA;; 2026.
SABIO-RK; P12996; -.
UniPathway; UPA00078; UER00162.
EvolutionaryTrace; P12996; -.
PRO; PR:P12996; -.
Proteomes; UP000000318; Chromosome.
Proteomes; UP000000625; Chromosome.
GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; IDA:EcoCyc.
GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:EcoCyc.
GO; GO:0004076; F:biotin synthase activity; IDA:EcoCyc.
GO; GO:0005506; F:iron ion binding; IEA:UniProtKB-UniRule.
GO; GO:0009102; P:biotin biosynthetic process; IMP:EcoCyc.
Gene3D;; -; 1.
HAMAP; MF_01694; BioB; 1.
InterPro; IPR013785; Aldolase_TIM.
InterPro; IPR010722; BATS_dom.
InterPro; IPR002684; Biotin_synth/BioAB.
InterPro; IPR024177; Biotin_synthase.
InterPro; IPR006638; Elp3/MiaB/NifB.
InterPro; IPR007197; rSAM.
PANTHER; PTHR22976; PTHR22976; 1.
Pfam; PF06968; BATS; 1.
Pfam; PF04055; Radical_SAM; 1.
PIRSF; PIRSF001619; Biotin_synth; 1.
SFLD; SFLDF00272; biotin_synthase; 1.
SMART; SM00876; BATS; 1.
SMART; SM00729; Elp3; 1.
TIGRFAMs; TIGR00433; bioB; 1.
1: Evidence at protein level;
2Fe-2S; 3D-structure; 4Fe-4S; Biotin biosynthesis; Complete proteome;
Direct protein sequencing; Iron; Iron-sulfur; Metal-binding;
Reference proteome; S-adenosyl-L-methionine; Transferase.
CHAIN 1 346 Biotin synthase.
METAL 53 53 Iron-sulfur 1 (4Fe-4S-S-AdoMet).
METAL 57 57 Iron-sulfur 1 (4Fe-4S-S-AdoMet).
METAL 60 60 Iron-sulfur 1 (4Fe-4S-S-AdoMet).
METAL 97 97 Iron-sulfur 2 (2Fe-2S).
METAL 128 128 Iron-sulfur 2 (2Fe-2S).
METAL 188 188 Iron-sulfur 2 (2Fe-2S).
METAL 260 260 Iron-sulfur 2 (2Fe-2S).
MUTAGEN 53 53 C->A: Total loss of activity.
MUTAGEN 57 57 C->A: Total loss of activity.
MUTAGEN 60 60 C->A: Total loss of activity.
MUTAGEN 97 97 C->A: Total loss of activity.
MUTAGEN 128 128 C->A: Total loss of activity.
MUTAGEN 151 151 N->A: Total loss of activity.
MUTAGEN 152 152 H->A: Weak activity.
MUTAGEN 153 153 N->A: Total loss of activity.
MUTAGEN 155 155 D->A: Total loss of activity.
MUTAGEN 188 188 C->A: Total loss of activity.
CONFLICT 63 63 S -> T (in Ref. 1; AAA23515).
TURN 10 12 {ECO:0000244|PDB:1R30}.
HELIX 13 17 {ECO:0000244|PDB:1R30}.
HELIX 20 34 {ECO:0000244|PDB:1R30}.
STRAND 41 49 {ECO:0000244|PDB:1R30}.
STRAND 53 55 {ECO:0000244|PDB:1R30}.
HELIX 78 90 {ECO:0000244|PDB:1R30}.
STRAND 94 100 {ECO:0000244|PDB:1R30}.
TURN 107 109 {ECO:0000244|PDB:1R30}.
HELIX 110 122 {ECO:0000244|PDB:1R30}.
STRAND 125 130 {ECO:0000244|PDB:1R30}.
HELIX 136 145 {ECO:0000244|PDB:1R30}.
STRAND 149 151 {ECO:0000244|PDB:1R30}.
HELIX 158 164 {ECO:0000244|PDB:1R30}.
HELIX 170 184 {ECO:0000244|PDB:1R30}.
STRAND 186 188 {ECO:0000244|PDB:1R30}.
STRAND 191 193 {ECO:0000244|PDB:1R30}.
HELIX 199 210 {ECO:0000244|PDB:1R30}.
STRAND 211 214 {ECO:0000244|PDB:1R30}.
STRAND 217 223 {ECO:0000244|PDB:1R30}.
HELIX 240 253 {ECO:0000244|PDB:1R30}.
STRAND 257 264 {ECO:0000244|PDB:1R30}.
HELIX 265 267 {ECO:0000244|PDB:1R30}.
HELIX 270 279 {ECO:0000244|PDB:1R30}.
STRAND 283 285 {ECO:0000244|PDB:1R30}.
STRAND 287 294 {ECO:0000244|PDB:1R30}.
HELIX 298 307 {ECO:0000244|PDB:1R30}.
SEQUENCE 346 AA; 38648 MW; 550A7899A2DF6082 CRC64;

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Pathways :
WP1403: AMPK signaling
WP1422: Sphingolipid Metabolism
WP1423: Ganglio Sphingolipid Metabolism
WP1424: Globo Sphingolipid Metabolism
WP1461: Photosynthetic Carbon Reduction
WP1621: Arginine and proline metabolism
WP1631: Biotin metabolism
WP1708: Terpenoid backbone biosynthesis
WP2199: Seed Development
WP2208: Cardiolipin Biosynthesis
WP2210: Oryzalexin S biosynthesis
WP2211: Geranylgeranyldiphosphate biosynthesis II (plastidic)
WP2248: anthocyanin biosynthesis
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP2345: vitamin B7 (biotin) biosynthesis pathway
WP296: TCA Cycle - biocyc
WP626: Abscisic Acid Biosynthesis
WP668: Octadecanoid Pathway
WP677: Momilactone biosynthesis

Related Genes :
[al-3 B8P8.010 NCU01427] Geranylgeranyl pyrophosphate synthase (GGPP synthase) (GGPPSase) (EC 2.5.1.-) ((2E,6E)-farnesyl diphosphate synthase) (Albino-3 protein) (Dimethylallyltranstransferase) (EC (Farnesyl diphosphate synthase) (Farnesyltranstransferase) (EC (Geranylgeranyl diphosphate synthase) (Geranyltranstransferase) (EC
[ACC1 ABP2 FAS3 MTR7 YNR016C N3175] Acetyl-CoA carboxylase (ACC) (EC (Fatty acid synthetase 3) (mRNA transport-defective protein 7) [Includes: Biotin carboxylase (EC]
[pyrG A6592_02570 A8M42_16405 A9R57_06965 AC067_22330 AC789_1c31020 ACN002_2797 ACN77_07080 ACN81_20385 ACU57_24415 ACU90_23015 AJ318_22735 AKG99_03555 AM270_00945 AM446_06950 AM464_05605 AM465_10605 AML07_12460 AML35_05300 APT94_17890 APU18_18535 APZ14_09290 ARC77_10140 AU473_08010 AUQ13_17535 AUS26_15660 AW059_10675 AW106_00665 AWP75_20610 AZZ83_003241 B1K96_20050 B7C53_10055 B9M99_21725 B9N33_09475 B9T59_19685 BB545_13920 BE963_03670 BEN53_16995 BET08_07180 BH694_13410 BHF46_05050 BHS81_16640 BHS87_15735 BIQ87_15835 BIU72_09520 BIZ41_16885 BJJ90_05265 BK248_12970 BK292_23205 BK334_11935 BK373_15870 BK375_10085 BK383_11680 BK400_05820 BMT49_17330 BMT53_21250 BMT91_11105 BN17_26661 BTQ04_11510 BTQ06_23845 BUE81_06975 BVL39_12970 BW690_04975 BWP17_05185 BXT93_24405 BZL31_00820 BZL69_02125 C1I57_04860 C2M16_17770 C2U48_20025 C3K24_08940 C4J69_11655 C4K41_05275 C4M78_00835 C5715_23540 C5N07_06155 C5P01_05005 C5P43_15935 C5P44_09340 C6669_14670 C6986_17750 C6B13_03370 C7235_05745 C7B02_19400 C7B06_11630 C7B07_14530 C7B08_01430 C9E25_03325 CA593_12975 CCZ14_04445 CCZ17_10850 CDL37_13440 CG691_07365 CG692_07005 CG705_05530 CG706_07860 CIJ94_12220 COD30_01795 COD46_07095 CR538_05495 CR539_18815 CRE06_03485 CRM83_26360 CSB64_15850 CT143_09630 CT146_00680 CV83915_03339 CVH05_06295 CWM24_00790 CWS33_03125 CXB56_08765 D0X26_06660 D1900_12730 D2183_19100 D2F89_14380 D3I61_16000 DD762_13665 DIV22_29760 DIV25_29790 DL545_05995 DL800_20505 DNQ41_18960 DNR41_08670 DQE83_04685 DS732_20695 DS966_06010 DTL43_09355 DTL84_00105 DTL90_02675 DTM10_03745 DTM25_22630 DTM27_13675 DTM45_13530 EC1094V2_904 EC3234A_48c00890 EC95NR1_02021 ECONIH1_15890 ECs3640 EL75_0914 EL79_0915 EL80_0918 ERS085365_02427 ERS085366_03042 ERS085374_03279 ERS085386_03410 ERS085416_02898 ERS139211_02072 ERS150873_02003 ERS150876_01467 FORC28_1110 GJ11_18025 HMPREF3040_01161 HW43_18180 JD73_16335 MJ49_17095 MS6198_30910 MS8345_02965 NCTC10082_03473 NCTC10090_04050 NCTC10418_01701 NCTC10764_00296 NCTC10766_00690 NCTC10767_02309 NCTC11022_02860 NCTC11112_00121 NCTC11181_03277 NCTC12950_01251 NCTC13125_04353 NCTC13127_01436 NCTC13462_04807 NCTC13846_01212 NCTC7152_00995 NCTC7927_01209 NCTC8500_01090 NCTC8960_03783 NCTC9007_03892 NCTC9010_01168 NCTC9036_01135 NCTC9037_01243 NCTC9045_01221 NCTC9050_04166 NCTC9058_00847 NCTC9062_02131 NCTC9075_01630 NCTC9077_01409 NCTC9081_05851 NCTC9117_01609 NCTC9119_01271 NCTC9434_01004 NCTC9706_03296 NCTC9775_04845 NCTC9777_02704 NCTC9969_01292 PU06_02080 RG28_07675 RK56_023165 SAMEA3472033_01264 SAMEA3472044_02272 SAMEA3472047_00339 SAMEA3472056_05455 SAMEA3472067_02540 SAMEA3472070_01673 SAMEA3472080_03155 SAMEA3472090_00131 SAMEA3472108_00527 SAMEA3472110_03462 SAMEA3472112_03722 SAMEA3472114_02432 SAMEA3472147_03296 SAMEA3484427_03298 SAMEA3484429_03415 SAMEA3484433_01660 SAMEA3484434_01581 SAMEA3485101_02257 SAMEA3485113_02257 SAMEA3752372_03639 SAMEA3752557_03040 SAMEA3752559_02995 SAMEA3752620_01282 SAMEA3753064_02287 SAMEA3753097_02219 SAMEA3753106_03183 SAMEA3753164_01192 SAMEA3753290_02847 SAMEA3753300_01107 SAMEA3753391_02580 SAMEA3753397_04005 SK85_03024 SY51_15605 UC41_20365 UN91_03645 WM48_14990 WQ89_10170 WR15_06090 YDC107_1339] CTP synthase (EC (Cytidine 5'-triphosphate synthase) (Cytidine triphosphate synthetase) (CTP synthetase) (CTPS) (UTP--ammonia ligase)
[TTHA1582] 8-amino-7-oxononanoate synthase/2-amino-3-ketobutyrate coenzyme A ligase (AONS/AKB ligase) (EC (EC (7-keto-8-amino-pelargonic acid synthase) (7-KAP synthase) (KAPA synthase) (8-amino-7-ketopelargonate synthase) (Alpha-oxoamine synthase) (Glycine acetyltransferase)
[Acacb Acc2 Accb] Acetyl-CoA carboxylase 2 (EC (ACC-beta) [Includes: Biotin carboxylase (EC]
[hchA A8C65_13880 A9R57_25255 AKG99_20940 AMK83_16550 B7C53_22525 B9M99_11580 B9T59_01945 BJJ90_15205 BMT49_12710 BMT53_00170 BUE81_10670 BW690_17225 BZL69_29425 C2U48_24800 C5715_19445 C5N07_21380 C6669_19295 C7B06_02290 C7B07_03930 CDL37_00765 CG691_19145 CG705_13560 CG706_14580 CIJ94_05515 COD46_23180 CRD98_26150 D3I61_11545 DL800_09215 DNQ41_14245 DQE83_22775 DTL43_21780 DTL84_23375 DTM25_06080 EC95NR1_00961 ERS085379_01273 ERS085386_05041 HMPREF3040_01583 HW43_13705 NCTC10082_04431 NCTC10418_03071 NCTC10767_03558 NCTC11022_01867 NCTC11126_04427 NCTC11181_05650 NCTC12950_02263 NCTC13462_05714 NCTC8985_00529 NCTC9111_05933 NCTC9703_00277 PU06_24500 SAMEA3472055_03589 SAMEA3472056_01268 SAMEA3472070_00654 SAMEA3472080_04213 SAMEA3472090_03376 SAMEA3472110_00060 SAMEA3472112_00448 SAMEA3752372_00752 SAMEA3753106_00003 SAMEA3753391_00513 UN91_23615 WQ89_10695] Protein/nucleic acid deglycase HchA (EC 3.1.2.-) (EC 3.5.1.-) (EC (Maillard deglycase)
[HLCS] Biotin--protein ligase (EC 6.3.4.-) (Biotin apo-protein ligase) [Includes: Biotin--[methylmalonyl-CoA-carboxytransferase] ligase (EC; Biotin--[propionyl-CoA-carboxylase [ATP-hydrolyzing]] ligase (EC (Holocarboxylase synthetase) (HCS); Biotin--[methylcrotonoyl-CoA-carboxylase] ligase (EC; Biotin--[acetyl-CoA-carboxylase] ligase (EC]
[aro-1 aro-2 aro-4 aro-5 aro-9 B14H13.20 NCU016321] Pentafunctional AROM polypeptide [Includes: 3-dehydroquinate synthase (DHQS) (EC; 3-phosphoshikimate 1-carboxyvinyltransferase (EC (5-enolpyruvylshikimate-3-phosphate synthase) (EPSP synthase) (EPSPS); Shikimate kinase (SK) (EC; 3-dehydroquinate dehydratase (3-dehydroquinase) (EC; Shikimate dehydrogenase (EC]
[al-2 B22I21.230 NCU00585] Bifunctional lycopene cyclase/phytoene synthase (Protein albino-2) [Includes: Lycopene beta-cyclase (EC (Carotene cyclase) (Lycopene cyclase); Phytoene synthase (EC]
[agaY agaY_1 agaY_2 kbaY kbaY_1 kbaY_2 A6581_06135 A6592_14490 A8C65_02445 A8G17_24215 A9819_18030 A9R57_12875 AC789_1c35070 ACN002_3231 ACN81_18735 ACU57_14720 ACU90_11840 AKG99_18810 AM270_10360 AM446_04575 AM464_08310 AMK83_06615 AML07_27945 AML35_14160 APT94_22945 APU18_16660 APZ14_04020 ARC77_12125 AU473_06025 AUQ13_02800 AUS26_18535 AW059_15450 AZZ83_001415 B1K96_05960 B7C53_19450 BB545_10055 BEN53_19445 BHF46_07040 BHS81_18925 BIZ41_14335 BJJ90_03045 BK248_21775 BK292_10495 BK334_09815 BK383_15710 BK400_20325 BMT49_25850 BMT53_18450 BN17_30821 BTQ04_16760 BTQ06_20745 BVL39_10420 BW690_01005 BWP17_07060 BXT93_18380 BZL31_25275 BZL69_07435 C2U48_17840 C3K24_11445 C4J69_18785 C4K41_03525 C5715_12280 C5N07_16465 C5P01_19110 C5P43_02160 C6669_12295 C6986_20200 C6B13_15150 C7235_03500 C7B02_08945 C7B06_16525 C7B07_10875 C7B08_03310 C9E25_21030 CA593_10600 CG691_12975 CG692_22965 CG705_12120 CG706_23220 COD30_05970 COD46_22025 CR538_03350 CR539_20970 CRD98_04990 CRE06_06550 CRM83_23775 CSB64_06340 CT143_11135 CT146_02800 CVH05_07665 CWS33_08100 CXB56_06685 D0X26_08835 D1900_24065 D2183_08305 D2F89_23160 D3I61_18805 DIV22_09280 DIV25_06765 DL545_03915 DL800_22990 DNQ41_21475 DNR41_10930 DQE83_16800 DTL43_04020 DTL84_11155 DTL90_07295 DTM27_04405 DTM45_14255 EC1094V2_507 EC3234A_53c00160 EC95NR1_02516 ECONIH1_18600 ECs4017 EL75_0549 EL79_0572 EL80_0564 ERS085365_00596 ERS085366_00607 ERS085374_01873 ERS085379_00428 ERS085383_00753 ERS085386_00541 ERS085404_02243 ERS085406_03651 ERS085416_00299 ERS139211_00539 ERS150873_01748 ERS150876_00972 FORC28_0668 HMPREF3040_01995 HW43_20655 JD73_01650 MS6198_36220 MS8345_03490 NCTC10082_03001 NCTC10764_04039 NCTC10767_01694 NCTC10865_00851 NCTC11022_03300 NCTC11341_01695 NCTC12950_00651 NCTC13125_03918 NCTC13148_03216 NCTC13462_04280 NCTC13846_00667 NCTC7152_00616 NCTC8009_01738 NCTC8622_00268 NCTC8960_03245 NCTC8985_05190 NCTC9036_00713 NCTC9037_00830 NCTC9045_00750 NCTC9050_03774 NCTC9055_02547 NCTC9062_02519 NCTC9111_01031 NCTC9117_00956 NCTC9119_00687 NCTC9434_00595 NCTC9701_00743 NCTC9703_05134 NCTC9706_02907 NCTC9969_00822 PU06_20125 RG28_20800 RK56_014885 RX35_04224 SAMEA3472033_00859 SAMEA3472044_03367 SAMEA3472047_01838 SAMEA3472055_00433 SAMEA3472056_03039 SAMEA3472067_02761 SAMEA3472070_01205 SAMEA3472080_00912 SAMEA3472108_00133 SAMEA3472110_01572 SAMEA3472112_01556 SAMEA3472114_00516 SAMEA3472147_03318 SAMEA3484427_00641 SAMEA3484429_00701 SAMEA3484433_01239 SAMEA3484434_03283 SAMEA3485101_01677 SAMEA3752372_01750 SAMEA3752557_01908 SAMEA3752559_03865 SAMEA3753064_02903 SAMEA3753097_03267 SAMEA3753106_03728 SAMEA3753290_00181 SAMEA3753300_02165 SAMEA3753391_02230 SAMEA3753397_00141 SK85_03447 UC41_11540 UN86_15655 WM48_17485 WQ89_06915 WR15_24715 YDC107_1814] D-tagatose-1,6-bisphosphate aldolase subunit KbaY (TBPA) (TagBP aldolase) (EC (D-tagatose-bisphosphate aldolase class II) (Ketose 1,6-bisphosphate aldolase class II) (Tagatose-bisphosphate aldolase)
[Nos2 Inosl] Nitric oxide synthase, inducible (EC (Inducible NO synthase) (Inducible NOS) (iNOS) (Macrophage NOS) (MAC-NOS) (NOS type II) (Peptidyl-cysteine S-nitrosylase NOS2)
[ST8SIA1 SIAT8 SIAT8A] Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase (EC (Alpha-2,8-sialyltransferase 8A) (Ganglioside GD3 synthase) (Ganglioside GT3 synthase) (Sialyltransferase 8A) (SIAT8-A) (Sialyltransferase St8Sia I) (ST8SiaI)
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC (EC (EC (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC (NS5B) (p68)]
[dim-5 29E8.110 NCU04402] Histone-lysine N-methyltransferase, H3 lysine-9 specific dim-5 (EC (Histone H3-K9 methyltransferase dim-5) (H3-K9-HMTase dim-5) (HKMT)
[st8sia1 siat8a] Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase (EC (Alpha-2,8-sialyltransferase 8A) (Ganglioside GD3 synthase) (XlGD3 synthase) (Sialyltransferase 8A) (SIAT8-A) (Sialyltransferase St8Sia I) (ST8SiaI)
[HFA1 EC1118_1M3_4049g] Acetyl-CoA carboxylase, mitochondrial (ACC) (EC [Includes: Biotin carboxylase (EC]
[iscS iscS_1 A6581_02145 A6592_14885 A8C65_03965 A8G17_10685 A8M42_18685 A9819_14635 A9R57_16930 AC067_03015 AC789_1c28660 ACN77_09430 ACN81_26435 ACU57_06285 ACU90_01375 AJ318_26005 AKG99_22280 AM270_07100 AM446_08145 AM464_04450 AM465_11700 AMK83_11225 AML07_10540 AML35_21525 APT94_12335 APU18_00295 APZ14_05615 ARC77_08945 AU473_09315 AUQ13_13105 AUS26_21555 AW059_05940 AW106_10960 AWP75_00135 AZZ83_002723 B1K96_17760 B7C53_13290 B9M99_15840 B9N33_21250 B9T59_21105 BE963_28425 BEN53_15845 BER14_02655 BET08_22520 BH694_10200 BHF46_00575 BHS81_15460 BHS87_14335 BIQ87_14690 BIU72_16435 BIZ41_13705 BJJ90_06620 BK248_16700 BK292_20650 BK334_04895 BK373_05915 BK375_00880 BK383_22845 BK400_09035 BMR23_12730 BMT49_16180 BMT53_23050 BMT91_09840 BTQ04_10030 BTQ06_16545 BUE81_08125 BVL39_14165 BW690_04500 BWP17_17035 BZL31_13665 BZL69_10285 C1I57_24205 C2M16_05920 C2U48_21435 C3K24_07520 C4J69_10615 C4K41_12560 C4M78_10890 C5N07_10225 C5P01_05670 C5P43_04165 C5P44_15165 C6669_16070 C6986_16375 C6B13_21190 C7235_06915 C7B02_18515 C7B06_11270 C7B07_12285 C7B08_05430 CA593_14170 CCZ14_18705 CCZ17_22060 CDL37_24785 CG691_06060 CG692_02695 CG705_05185 CG706_03765 CIJ94_05825 COD30_00935 COD46_11390 CR539_17655 CRD98_15000 CRE06_08785 CRM83_27605 CSB64_12500 CT143_05820 CT146_18385 CV83915_03587 CVH05_18115 CWM24_13125 CWS33_10120 CXB56_09960 D0X26_11620 D1900_21335 D2183_14465 D2F89_15600 D3I61_14705 DD762_08545 DIV22_32035 DIV25_09780 DL545_07355 DL800_19085 DNQ41_17815 DNR41_15780 DQE83_18635 DS732_18775 DS966_02860 DTL43_01800 DTL84_06515 DTL90_08325 DTM10_01260 DTM25_14855 DTM27_14340 DTM45_09080 EC1094V2_1138 EC3234A_44c01370 EC95NR1_01752 ECONIH1_14765 EL75_1117 EL79_1128 EL80_1131 ERS085365_01538 ERS085366_02045 ERS085374_00061 ERS085379_00921 ERS085383_02049 ERS085386_03188 ERS085404_01057 ERS085406_03472 ERS085411_02202 ERS085416_01266 ERS139211_00888 ERS150873_01415 ERS150876_00833 FORC28_1424 HW43_17050 JD73_17725 MJ49_18275 MS6198_28580 MS8345_02723 NCTC10090_04376 NCTC10766_01180 NCTC10767_02594 NCTC11181_03575 NCTC11341_00889 NCTC12950_01537 NCTC13125_04632 NCTC13462_05052 NCTC13846_01437 NCTC7152_01285 NCTC7922_00893 NCTC7927_01500 NCTC7928_01371 NCTC8009_03115 NCTC8179_04409 NCTC8450_04290 NCTC8500_01442 NCTC8621_01401 NCTC8959_02462 NCTC8960_04060 NCTC8985_06161 NCTC9007_03642 NCTC9010_01409 NCTC9036_01412 NCTC9037_01482 NCTC9045_01545 NCTC9050_04644 NCTC9055_03293 NCTC9058_00608 NCTC9062_01792 NCTC9073_04547 NCTC9075_01973 NCTC9111_01941 NCTC9119_01524 NCTC9434_01284 NCTC9701_01429 NCTC9703_01091 NCTC9706_04616 NCTC9775_05141 NCTC9777_02572 NCTC9962_00698 NCTC9969_01533 PU06_05300 RG28_09220 RK56_021935 RX35_01423 SAMEA3472033_00658 SAMEA3472044_02985 SAMEA3472047_01032 SAMEA3472055_00937 SAMEA3472056_00874 SAMEA3472070_00065 SAMEA3472080_01607 SAMEA3472090_01244 SAMEA3472108_03497 SAMEA3472110_00486 SAMEA3472112_00780 SAMEA3472114_03249 SAMEA3472147_00165 SAMEA3484427_00440 SAMEA3484429_00549 SAMEA3484433_03192 SAMEA3484434_00296 SAMEA3485101_04492 SAMEA3485113_03372 SAMEA3752372_01122 SAMEA3752557_00969 SAMEA3752559_00692 SAMEA3752620_00062 SAMEA3753064_03100 SAMEA3753097_02751 SAMEA3753106_01137 SAMEA3753164_00628 SAMEA3753290_03552 SAMEA3753300_01026 SAMEA3753391_02715 SAMEA3753397_00908 SK85_02782 SY51_14535 UC41_13245 UN91_26515 WM48_13555 WQ89_05730 WR15_01190 YDC107_1108] Cysteine desulfurase IscS (EC
[ACC1 EMB22 GK PAS3 At1g36160 F15C21.1] Acetyl-CoA carboxylase 1 (AtACC1) (EC (Protein EMBRYO DEFECTIVE 22) (Protein GURKE) (Protein PASTICCINO 3) [Includes: Biotin carboxylase (EC]
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC (EC (EC (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC (NS5B) (p68)]
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC (EC (EC (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC (NS5B) (p68)]
[yjbN dusA A6581_03815 A9819_23140 AC789_1c44580 ACN77_13265 ACN81_05795 AW059_18320 B1K96_03640 B7C53_20030 B9M99_07285 B9T59_11200 BB545_04715 BE963_11655 BHS81_24320 BIU72_20630 BN17_40231 BTQ06_28285 BUE81_22495 BVL39_04970 BWP17_09085 BXT93_20165 BZL69_05000 C2U48_12360 C4J69_17345 C4M78_06330 C5N07_20225 C5P01_10975 C5P43_26750 C6669_07250 C7235_23350 C7B02_13830 CA593_05650 CG691_24515 CG705_24980 CG706_06955 CIJ94_13445 COD46_18670 CR538_23810 CRD98_24950 CRM83_18265 CVH05_02240 CWS33_16005 CXB56_26125 D0X26_12230 D3I61_23865 DD762_09595 DL545_23295 DNQ41_01750 DQE83_12890 DS732_01940 DTL84_03985 EC3234A_77c00420 EL75_4140 EL79_4345 EL80_4252 ERS085374_01630 ERS085383_01453 ERS085404_01248 HMPREF3040_01367 NCTC10090_02700 NCTC10418_07037 NCTC10764_02883 NCTC10865_05778 NCTC11112_02403 NCTC11181_01881 NCTC11341_02874 NCTC12950_05132 NCTC7152_04647 NCTC7927_05171 NCTC8450_00470 NCTC8985_03929 NCTC9010_04826 NCTC9037_04708 NCTC9045_05465 NCTC9050_02741 NCTC9062_03523 NCTC9077_05824 NCTC9701_04921 NCTC9775_03044 NCTC9777_01046 RK56_017030 RX35_03830 SAMEA3472055_01598 SAMEA3472067_03766 SAMEA3472108_01690 SAMEA3472114_02034 SAMEA3472147_04808 SAMEA3484427_03836 SAMEA3484429_02481 SAMEA3752559_00279 SAMEA3753064_01454 SAMEA3753290_01943 SAMEA3753300_00780] tRNA-dihydrouridine(20/20a) synthase (EC 1.3.1.-) (EC (U20-specific dihydrouridine synthase) (U20-specific Dus) (tRNA-dihydrouridine synthase A)
[rep 1a-1b] Replicase polyprotein 1ab (ORF1ab polyprotein) [Cleaved into: Nsp1 (EC 3.4.22.-); Nsp1-alpha papain-like cysteine proteinase (EC 3.4.22.-) (PCP1-alpha); Nsp1-beta papain-like cysteine proteinase (EC 3.4.22.-) (PCP1-beta); Nsp2 cysteine proteinase (EC (EC 3.4.22.-) (CP2) (CP); Non-structural protein 3 (Nsp3); Serine protease nsp4 (3CLSP) (EC 3.4.21.-) (3C-like serine proteinase) (Nsp4); Non-structural protein 5-6-7 (Nsp5-6-7); Non-structural protein 5 (Nsp5); Non-structural protein 6 (Nsp6); Non-structural protein 7-alpha (Nsp7-alpha); Non-structural protein 7-beta (Nsp7-beta); Non-structural protein 8 (Nsp8); RNA-directed RNA polymerase (Pol) (RdRp) (EC (Nsp9); Helicase nsp10 (Hel) (EC (EC (Nsp10); Non-structural protein 11 (Nsp11); Non-structural protein 12 (Nsp12)]
[ribH2 ribH-2 BAB2_0545] 6,7-dimethyl-8-ribityllumazine synthase 2 (DMRL synthase 2) (LS 2) (Lumazine synthase 2) (EC (BLS) (Type II lumazine synthase)
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC (EC (EC (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC (NS5B) (p68)]
[] Genome polyprotein [Cleaved into: Core protein p21 (Capsid protein C) (p21); Core protein p19; Envelope glycoprotein E1 (gp32) (gp35); Envelope glycoprotein E2 (NS1) (gp68) (gp70); p7; Protease NS2-3 (p23) (EC 3.4.22.-); Serine protease NS3 (EC (EC (EC (Hepacivirin) (NS3P) (p70); Non-structural protein 4A (NS4A) (p8); Non-structural protein 4B (NS4B) (p27); Non-structural protein 5A (NS5A) (p56); RNA-directed RNA polymerase (EC (NS5B) (p68)]
[ribBA ribH GA0115236_158411] Multifunctional fusion protein [Includes: Riboflavin biosynthesis protein RibBA; 3,4-dihydroxy-2-butanone 4-phosphate synthase (DHBP synthase) (EC; GTP cyclohydrolase-2 (EC (GTP cyclohydrolase II); 6,7-dimethyl-8-ribityllumazine synthase (DMRL synthase) (LS) (Lumazine synthase) (EC]
[lon lon_1 lon_2 A6581_06540 A8C65_09155 A8G17_09470 A8M42_12205 A9819_02150 A9R57_08730 AC067_13940 AC789_1c04390 ACN77_08400 ACN81_24745 ACU57_11790 ACU90_20700 AJ318_07395 AM270_02090 AM446_21265 AM464_19190 AM465_24425 AMK83_09080 AML07_05605 AML35_17195 APT94_11405 APU18_24755 APZ14_19130 AUQ13_18305 AUS26_08525 AW059_13755 AW106_10030 AWP75_24635 AZZ83_000203 B1K96_09680 B7C53_07945 B9M99_03985 B9N33_08900 B9T59_05700 BB545_15795 BE963_16350 BER14_14325 BET08_18215 BH694_02335 BHF46_21220 BHS81_02650 BIQ87_02425 BIU72_03070 BIZ41_19875 BJJ90_20055 BK248_01840 BK292_14395 BK334_05695 BK373_01080 BK375_01675 BK383_14710 BK400_22925 BMR23_09445 BMT49_03495 BMT53_08160 BMT91_05050 BN17_02431 BTQ06_01040 BUE81_06550 BVL39_00620 BW690_06825 BXT93_14065 BZL31_10455 BZL69_16545 C1I57_02830 C2M16_02950 C4J69_09250 C4M78_17970 C5715_07650 C5N07_12995 C5P01_16055 C5P43_02540 C6669_02490 C6986_02640 C6B13_10210 C7235_18620 C7B06_13115 C7B07_14925 C7B08_06455 C9E25_04330 CA593_00935 CCZ14_02195 CCZ17_03875 CDL37_08925 CG692_04795 CG705_03025 CG706_02860 CIJ94_10835 COD30_15795 COD46_04600 CR538_19245 CR539_06435 CRD98_01930 CSB64_03555 CT143_00390 CT146_15985 CWM24_20160 CWS33_13550 CXB56_21765 D0X26_07675 D1900_17610 D2183_00880 D2F89_19370 D3I61_03100 DD762_17560 DIV22_26545 DIV25_28050 DL545_18880 DL800_04145 DNQ41_06120 DNQ45_04780 DQE83_14690 DS732_07170 DS966_18225 DTL43_07145 DTL84_16480 DTM10_06325 DTM25_22445 DTM45_11225 EC1094V2_3409 EC3234A_4c01080 EC95NR1_04662 ECONIH1_02385 ERS085365_02395 ERS085374_02327 ERS085379_01165 ERS085383_00971 ERS085406_02176 ERS085416_01921 ERS139211_01924 ERS150876_00617 FORC28_4645 GJ11_02625 HMPREF3040_03444 HW43_05825 MJ49_04235 MS6198_04430 MS8345_00443 NCTC10082_01029 NCTC10090_01830 NCTC10418_05598 NCTC10764_05303 NCTC10766_05771 NCTC11022_05186 NCTC11181_01095 NCTC13462_01885 NCTC13846_03631 NCTC7152_03832 NCTC7922_06176 NCTC7927_04214 NCTC7928_04997 NCTC8179_01705 NCTC8959_05066 NCTC8960_01264 NCTC9007_00214 NCTC9010_03874 NCTC9036_03791 NCTC9037_03909 NCTC9050_01704 NCTC9055_00655 NCTC9058_03169 NCTC9062_04515 NCTC9111_03927 NCTC9117_04741 NCTC9434_02860 NCTC9703_03170 NCTC9706_01065 NCTC9777_00122 NCTC9969_03979 PU06_02695 RG28_02630 RK56_026450 RX35_02110 SAMEA3472033_03457 SAMEA3472044_00416 SAMEA3472047_02150 SAMEA3472055_02113 SAMEA3472067_03237 SAMEA3472070_02234 SAMEA3472080_01763 SAMEA3472090_01765 SAMEA3472108_01909 SAMEA3472110_00680 SAMEA3472112_02916 SAMEA3484427_03496 SAMEA3484429_01936 SAMEA3484433_02327 SAMEA3485113_01252 SAMEA3752372_02700 SAMEA3752557_00263 SAMEA3752559_02850 SAMEA3752620_00833 SAMEA3753097_00463 SAMEA3753106_00484 SAMEA3753164_00266 SAMEA3753300_00505 SAMEA3753391_04072 SAMEA3753397_02130 SK85_00464 SY51_02300 UC41_11885 UN86_09160 UN91_18465 WM48_02515 WR15_04115 YDC107_3709] Lon protease (EC (ATP-dependent protease La)
[At3g14510 MOA2.15] Putative geranylgeranyl pyrophosphate synthase 8, chloroplastic (GGPP synthase 8) (GGPS8) (EC 2.5.1.-) ((2E,6E)-farnesyl diphosphate synthase 8) (Dimethylallyltranstransferase 8) (EC (Farnesyl diphosphate synthase 8) (Farnesyltranstransferase 8) (EC (Geranyltranstransferase 8) (EC
[] Genome polyprotein [Cleaved into: P3; Protein 3AB; P2; P1; Capsid protein VP0 (VP4-VP2); Capsid protein VP4 (P1A) (Virion protein 4); Capsid protein VP2 (P1B) (Virion protein 2); Capsid protein VP3 (P1C) (Virion protein 3); Capsid protein VP1 (P1D) (Virion protein 1); Protease 2A (P2A) (EC (Picornain 2A) (Protein 2A); Protein 2B (P2B); Protein 2C (P2C) (EC; Protein 3A (P3A); Viral protein genome-linked (VPg) (Protein 3B) (P3B); Protein 3CD (EC; Protease 3C (P3C) (EC; RNA-directed RNA polymerase (RdRp) (EC (3D polymerase) (3Dpol) (Protein 3D) (3D)]
[1a] Replicase polyprotein 1a (pp1a) (ORF1a polyprotein) [Cleaved into: Non-structural protein 1 (nsp1) (Leader protein); Non-structural protein 2 (nsp2) (p65 homolog); Non-structural protein 3 (nsp3) (EC (EC (PL2-PRO) (Papain-like proteinase) (PL-PRO) (SARS coronavirus main proteinase); Non-structural protein 4 (nsp4); 3C-like proteinase (3CL-PRO) (3CLp) (EC 3.4.22.-) (nsp5); Non-structural protein 6 (nsp6); Non-structural protein 7 (nsp7); Non-structural protein 8 (nsp8); Non-structural protein 9 (nsp9); Non-structural protein 10 (nsp10) (Growth factor-like peptide) (GFL); Non-structural protein 11 (nsp11)]

Bibliography :
[28942842] A green fluorescent protein-based assay for high-throughput ligand-binding studies of a mycobacterial biotin protein ligase.
[28454708] Functional characterisation of Burkholderia pseudomallei biotin protein ligase: A toolkit for anti-melioidosis drug development.
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