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Ligand (S)-2-Hydroxy-2-methyl-3-oxobutanoate

Basic Ligand Information

Molecular Structure

Pathway Source

Pathways

BRENDA

acetoin degradation, valine metabolism

KEGG

2-Oxocarboxylic acid metabolism, Biosynthesis of amino acids, Biosynthesis of secondary metabolites, Butanoate metabolism, C5-Branched dibasic acid metabolism, Pantothenate and CoA biosynthesis, Valine, leucine and isoleucine biosynthesis more

MetaCyc

L-valine biosynthesis, pyruvate fermentation to (R)-acetoin I, pyruvate fermentation to (R)-acetoin II, pyruvate fermentation to (S)-acetoin, pyruvate fermentation to isobutanol (engineered)

Show all BRENDA pathways known for (S)-2-Hydroxy-2-methyl-3-oxobutanoate

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Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (6 results)

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Show Natural Substrate (6 entries)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.86

(2S)-2-acetolactate + NADPH = (2R)-2,3-dihydroxyisovalerate + NADP+

762913

-

1.1.1.86

(S)-2-acetolactate + NADH + H+ = (R)-2,3-dihydroxyisovalerate + NAD+

731279

-

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NADP+

762913, 762924, 763730

-

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = (R)-2,3-dihydroxyisovalerate + NADP+

731279, 738219, 763320

-

4.1.1.5

(2S)-2-hydroxy-2-methyl-3-oxobutanoate = (3R)-3-hydroxybutan-2-one + CO2

746718, 749291, 726550, 746804, 748494, 749292, 747299, 747389, 746865

-

4.1.1.5

(S)-2-hydroxy-2-methyl-3-oxobutanoate = (R)-acetoin + CO2

650700, 652583, 651663, 653090

-

1.1.1.86

4 entries

4.1.1.5

2 entries

In Vivo Product in Enzyme-catalyzed Reactions (3 results)

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Show Natural Product (3 entries)

EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.86

(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+

0

-

1.1.1.86

(R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+

0

-

1.1.1.86

2 entries

2.2.1.6

pyruvate = (S)-2-acetolactate + CO2

0

-

Substrate in Enzyme-catalyzed Reactions (18 results)

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Show Substrate (18 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.382

(2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NAD+

732457

-

1.1.1.383

(2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NAD+

732457

-

1.1.1.383

(2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NADP+

732457

-

1.1.1.383

(S)-2-acetolactate + NADH + H+ = 2,3-dihydroxy-3-methylbutanoate + NAD+

738976, 739528

-

1.1.1.383

(S)-2-acetolactate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

738976, 739528

-

1.1.1.86

(2S)-2-acetolactate + NADH + H+ = (R)-2,3-dihydroxyisovalerate + NAD+

763172

-

1.1.1.86

(2S)-2-acetolactate + NADPH + H+ = (2R)-2,3-dihydroxyisovalerate + NADP+

762929, 762913

-

1.1.1.86

(2S)-2-acetolactate + NADPH + H+ = (R)-2,3-dihydroxyisovalerate + NADP+

763320, 762942, 763172

-

1.1.1.86

(2S)-2-acetolactate + NADPH + H+ = 3-hydroxy-3-methyl-2-oxobutyrate + NADP+

762676, 762999, 762924

-

1.1.1.86

(2S)-2-acetolactate + NADPH = (2R)-2,3-dihydroxyisovalerate + NADP+

762913

-

1.1.1.86

(S)-2-acetolactate + NADH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NAD+

763730

-

1.1.1.86

(S)-2-acetolactate + NADH + H+ = (R)-2,3-dihydroxyisovalerate + NAD+

763188, 731279, 737785

-

1.1.1.86

(S)-2-acetolactate + NADH + H+ = 2,3-dihydroxy-3-methylbutanoate + NAD+

739528

-

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = (2R)-2,3-dihydroxy-3-methylbutanoate + NADP+

762913, 762924, 763730

-

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = (R)-2,3-dihydroxyisovalerate + NADP+

763188, 731279, 737785, 738219, 763320

-

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

739528

-

4.1.1.5

(2S)-2-hydroxy-2-methyl-3-oxobutanoate = (3R)-3-hydroxybutan-2-one + CO2

746718, 749291, 726550, 746804, 748494, 749292, 747299, 747389, 746865

-

4.1.1.5

(S)-2-hydroxy-2-methyl-3-oxobutanoate = (R)-acetoin + CO2

650700, 701419, 651663, 652583, 653116, 651360, 702809, 653090, 649197

-

1.1.1.383

4 entries

1.1.1.86

11 entries

4.1.1.5

2 entries

Product in Enzyme-catalyzed Reactions (6 results)

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Show Product (6 entries)

EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.86

(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+

0

-

1.1.1.86

(R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH

0

-

1.1.1.86

(R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+

0

-

2.2.1.6

pyruvate = (S)-2-acetolactate + CO2

0

-

2.2.1.6

2 pyruvate = (S)-acetolactate + CO2

0

-

1.1.1.86

3 entries

2.2.1.6

2 entries

4.1.1.1

2 pyruvate = (S)-acetolactate + CO2

0

-

Enzyme Kinetic Parameters

k_cat Value (Turnover Number) (25 results)

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Show Turnover Number (25 entries)

EC NUMBER

TURNOVER NUMBER [1/S]

TURNOVER NUMBER MAXIMUM [1/S]

COMMENTARY

LITERATURE

1.1.1.86

0.00023

-

pH 8.0, 25°C

762924

1.1.1.86

0.00023

-

pH 8.0, 25°C

762924

1.1.1.86

0.011

-

pH 7.5, 55°C, 5 mM Mg2+, cofactor: NADH

763188

1.1.1.86

0.013

-

pH 7.5, 55°C, 5 mM Mg2+, cofactor: NADPH

763188

1.1.1.86

0.055

-

pH 8.0, 25°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.058

-

pH 8.0, 25°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.06

-

pH 8.0, 25°C, 10 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.068

-

pH 8.0, 25°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.157

-

pH 8.0, 37°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.164

-

pH 8.0, 37°C, 10 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.192

-

pH 8.0, 37°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.195

-

pH 8.0, 37°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.235

-

pH 8.0, 22°C

763172

1.1.1.86

0.444

-

pH 8.0, 60°C, 6 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.526

-

pH 8.0, 60°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.77

-

wild type enzyme, with NADPH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

0.876

-

pH 8.0, 60°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.957

-

pH 8.0, 60°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

1.09

-

wild type enzyme, with NADH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

1.3

-

mutant enzyme T84S, with NADH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

1.4

-

at pH 8.5 and 37°C

738219

1.1.1.86

3.7

-

pH 8.0, 25°C

762676

1.1.1.86

3.81

-

mutant enzyme T84S, with NADPH as cosubstrate, at pH 7.0 and 50°C

737785

4.1.1.5

0.7

-

pH 6

651360

4.1.1.5

66.67

-

pH 6

651360

1.1.1.86

23 entries

4.1.1.5

2 entries

K_M Value (25 results)

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Show KM Value (25 entries)

EC NUMBER

KM VALUE [MM]

KM VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

1.1.1.86

0.04

-

mutant enzyme T84S, with NADH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

0.06

-

pH 8.0, 60°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.074

-

pH 8.0, 37°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.08

-

wild type enzyme, with NADPH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

0.091

-

pH 8.0, 60°C, 6 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.093

-

pH 8.0, 60°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.099

-

pH 8.0, 37°C, 10 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.11

-

at pH 8.5 and 37°C

738219

1.1.1.86

0.14

-

pH 8.0, 25°C, 10 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.144

-

pH 8.0, 60°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.15

-

mutant enzyme T84S, with NADPH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

0.157

-

pH 8.0, 37°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.165

-

pH 8.0, 37°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.184

-

pH 8.0, 25°C, 2 mM Mg2+, cofactor: NADPH

763730

1.1.1.86

0.188

-

pH 8.0, 25°C, 10 mM Mg2+, cofactor: NADH

763730

1.1.1.86

0.24

-

wild type enzyme, with NADH as cosubstrate, at pH 7.0 and 50°C

737785

1.1.1.86

0.285

-

pH 8.0, 25°C

762924

1.1.1.86

0.285

-

pH 8.0, 25°C

762924

1.1.1.86

0.469

-

pH 8.0, 25°C, 2 mM Mg2+, cofactor: NADH

763730

1.1.1.86

2.16

-

pH 8.0, 22°C

763172

1.1.1.86

2.69

-

pH 7.5, 55°C, 5 mM Mg2+, cofactor: NADH

763188

1.1.1.86

4.43

-

pH 7.5, 55°C, 5 mM Mg2+, cofactor: NADPH

763188

1.1.1.86

6

-

pH 8.0, 25°C

762676

4.1.1.5

0.0177

-

at pH 6.0 and 45°C

746718

4.1.1.5

1.3

-

pH 6

651360

1.1.1.86

23 entries

4.1.1.5

2 entries

References & Links

Literature References (34)

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Show Reference (34 entries)

BRENDA REFERENCE ID

PUBMED ID

TITLE

YEAR

AUTHORS

JOURNAL

VOLUME

PAGES

649197

12777778

Purification, crystallization and preliminary X-ray crystallographic studies on acetolactate decarboxylase

2003

Najmudin, S.; Andersen, J.T.; Patkar, S.A.; Borchert, T.V.; Crout, D.H.G.; Fülöp, V.

Acta Crystallogr. Sect. D

59

1073-1075

650700

11101321

Improved performances and control of beer fermentation using encapsulated alpha-acetolactate decarboxylase and modeling

2000

Dulieu, C.; Moll, M.; Boudrant, J.; Poncelet, D.

Biotechnol. Prog.

16

958-965

651360

11164316

Purification and characterisation of acetolactate decarboxylase from Leuconostoc lactis NCW1

2001

O'Sullivan, S.M.; Condon, S.; Cogan, T.M.; Sheehan, D.

FEMS Microbiol. Lett.

194

245-249

651663

10986242

Transcriptional and translational regulation of alpha-acetolactate decarboxylase of Lactococcus lactis subsp. lactis

2000

Goupil-Feuillerat, N.; Corthier, G.; Godon, J.J.; Ehrlich, S.D.; Renault, P.

J. Bacteriol.

182

5399-5408

652583

16232430

Effect of alpha-acetolactate decarboxylase inactivation on alpha-acetolactate and diacetyl production by Lactococcus lactis subsp. lactis biovar diacetylactis

1999

Aymes, F.; Monnet, C.; Corrieu, G.

J. Biosci. Bioeng.

87

87-92

653090

12753249

Regulation of branched-chain amino acid biosynthesis by alpha-acetolactate decarboxylase in Streptococcus thermophilus

2003

Monnet, C.; Nardi, M.; Hols, P.; Gulea, M.; Corrieu, G.; Monnet, V.

Lett. Appl. Microbiol.

36

399-405

653116

10937822

Glucose/citrate cometabolism in Lactococcus lactis subsp. lactis biovar diacetylactis with impaired alpha-acetolactate decarboxylase

1999

Curic, M.; de Richelieu, M.; Henriksen, C.M.; Jochumsen, K.V.; Villadsen, J.; Nilsson, D.

Metab. Eng.

1

291-298

701419

-

Optimization and mechanism of diacetyl accumulation by Enterobacter aerogenes mutant UV-3

2009

Zhao, L.; Bao, Y.; Wang, J.; Liu, B.; An, L.

World J. Microbiol. Biotechnol.

25

57-64

702809

20213636

Metabolic engineering of acetoin and meso-2, 3-butanediol biosynthesis in E. coli

2010

Nielsen, D.R.; Yoon, S.H.; Yuan, C.J.; Prather, K.L.

Biotechnol. J.

5

274-284

726550

23985082

Structure and mechanism of acetolactate decarboxylase

2013

Marlow, V.A.; Rea, D.; Najmudin, S.; Wills, M.; Fueloep, V.

ACS Chem. Biol.

8

2339-2344

731279

25849365

Cofactor specificity motifs and the induced fit mechanism in Class I ketol-acid reductoisomerases

2015

Cahn, J.K.; Brinkmann-Chen, S.; Spatzal, T.; Wiig, J.A.; Buller, A.R.; Einsle, O.; Hu, Y.; Ribbe, M.W.; Arnold, F.H.

Biochem. J.

468

475-484

732457

25172159

Uncovering rare NADH-preferring ketol-acid reductoisomerases

2014

Brinkmann-Chen, S.; Cahn, J.K.; Arnold, F.H.

Metab. Eng.

26C

17-22

737785

25446654

Identification and optimization of a novel thermo- and solvent stable ketol-acid reductoisomerase for cell free isobutanol biosynthesis

2015

Reisse, S.; Garbe, D.; Brueck, T.

Biochimie

108

76-84

738219

26876563

Crystal structure of Mycobacterium tuberculosis ketol-acid reductoisomerase at 1.0 A resolution - a potential target for anti-tuberculosis drug discovery

2016

Lv, Y.; Kandale, A.; Wun, S.J.; McGeary, R.P.; Williams, S.J.; Kobe, B.; Sieber, V.; Schembri, M.A.; Schenk, G.; Guddat, L.W.

FEBS J.

283

1184-1196

738976

21515217

Engineered ketol-acid reductoisomerase and alcohol dehydrogenase enable anaerobic 2-methylpropan-1-ol production at theoretical yield in Escherichia coli

2011

Bastian, S.; Liu, X.; Meyerowitz, J.; Snow, C.; Chen, M.; Arnold, F.

Metab. Eng.

13

345-352

739528

23776225

General approach to reversing ketol-acid reductoisomerase cofactor dependence from NADPH to NADH

2013

Brinkmann-Chen, S.; Flock, T.; Cahn, J.; Snow, C.; Brustad, E.; McIntosh, J.; Meinhold, P.; Zhang, L.; Arnold, F.

Proc. Natl. Acad. Sci. USA

110

10946-10951

746718

25543264

Improving the acidic stability of Staphylococcus aureus alpha-acetolactate decarboxylase in Bacillus subtilis by changing basic residues to acidic residues

2015

Zhang, X.; Rao, Z.; Li, J.; Zhou, J.; Yang, T.; Xu, M.; Bao, T.; Zhao, X.

Amino Acids

47

707-717

746804

-

alpha-Acetolactate overexpression from glucose in the diacetyl producer Lactococcus lactis ssp. lactis bv. diacetylactis B2103, a natural mutant lacking alpha-acetolactate decarboxylase

2014

Serebrennikov, V.; Kotova, L.; Glazunov, A.

Appl. Biochem. Microbiol.

50

689-700

746865

29796971

Structural and enzymatic characterization of acetolactate decarboxylase from Bacillus subtilis

2018

Ji, F.; Li, M.; Feng, Y.; Wu, S.; Wang, T.; Pu, Z.; Wang, J.; Yang, Y.; Xue, S.; Bao, Y.

Appl. Microbiol. Biotechnol.

102

6479-6491

747299

27285575

Enhanced production of butanol and acetoin by heterologous expression of an acetolactate decarboxylase in Clostridium acetobutylicum

2016

Shen, X.; Liu, D.; Liu, J.; Wang, Y.; Xu, J.; Yang, Z.; Guo, T.; Niu, H.; Ying, H.

Biores. Technol.

216

601-606

747389

27623795

Surface-engineered Saccharomyces cerevisiae displaying alpha-acetolactate decarboxylase from Acetobacter aceti ssp xylinum

2016

Cejnar, R.; Hlozkova, K.; Kotrba, P.; Dostalek, P.

Biotechnol. Lett.

38

2145-2151

748494

25131383

Purification and characterization of alpha-acetolactate decarboxylase (ALDC) from newly isolated Lactococcus lactis DX

2015

Guo, Y.; Pan, D.; Ding, H.; Wu, Z.; Sun, Y.; Zeng, X.

J. Sci. Food Agric.

95

1655-1661

749291

-

Catalytic mechanism of acetolactate decarboxylase from Brevibacillus brevis towards both enantiomers of alpha-acetolactate

2016

Zhao, C.; Su, H.; Liu, Y.

RSC Adv.

6

80621-80629

749292

-

QM/MM calculations and MD simulations of acetolactate decarboxylase to reveal substrate R/S-acetolactate binding mode and stereoselective catalytic mechansim

2016

Zhuang, C.; Zheng, Q.

RSC Adv.

6

91852-91859

762676

32745463

Inhibition studies of ketol-acid reductoisomerases from pathogenic microorganisms

2020

Wun, S.J.; Johnson, L.A.; You, L.; McGeary, R.P.; Brueck, T.; Schenk, G.; Guddat, L.W.

Arch. Biochem. Biophys.

692

108516

762913

31309701

Mechanism and inhibitor exploration with binuclear Mg ketol-acid reductoisomerase targeting the biosynthetic pathway of branched-chain amino acids

2020

Yu, M.J.; Wu, J.; Chen, S.L.

ChemBioChem

21

381-391

762924

28975665

Crystal structures of Staphylococcus aureus ketol-acid reductoisomerase in complex with two transition state analogues that have biocidal activity

2017

Patel, K.M.; Teran, D.; Zheng, S.; Kandale, A.; Garcia, M.; Lv, Y.; Schembri, M.A.; McGeary, R.P.; Schenk, G.; Guddat, L.W.

Chemistry

23

18289-18295

762929

33215746

Discovery of a pyrimidinedione derivative with potent inhibitory activity against Mycobacterium tuberculosis ketol-acid reductoisomerase

2021

Lin, X.; Kurz, J.L.; Patel, K.M.; Wun, S.J.; Hussein, W.M.; Lonhienne, T.; West, N.P.; McGeary, R.P.; Schenk, G.; Guddat, L.W.

Chemistry

27

3130-3141

762942

-

Crystal structure of ILvC, a ketol-acid reductoisomerase, from Streptococcus pneumoniae

2019

Kim, G.; Shin, D.; Lee, S.; Yun, J.; Lee, S.

Crystals

9

551

762999

32171154

Design and development of ((4-methoxyphenyl)carbamoyl) (5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl)amide analogues as Mycobacterium tuberculosis ketol-acid reductoisomerase inhibitors

2020

Krishna, V.S.; Zheng, S.; Rekha, E.M.; Nallangi, R.; Sai Prasad, D.V.; George, S.E.; Guddat, L.W.; Sriram, D.

Eur. J. Med. Chem.

193

112178

763172

31298526

Crystal structure and biochemical characterization of ketol-acid reductoisomerase from Corynebacterium glutamicum

2019

Lee, D.; Hong, J.; Kim, K.J.

J. Agric. Food Chem.

67

8527-8535

763188

30921515

Use of cryo-EM To uncover structural bases of pH effect and cofactor bispecificity of ketol-acid reductoisomerase

2019

Chen, C.Y.; Chang, Y.C.; Lin, B.L.; Lin, K.F.; Huang, C.H.; Hsieh, D.L.; Ko, T.P.; Tsai, M.D.

J. Am. Chem. Soc.

141

6136-6140

763320

30666485

Discovery and evaluation of novel Mycobacterium tuberculosis ketol-acid reductoisomerase inhibitors as therapeutic drug leads

2019

Krishna, V.S.; Zheng, S.; Rekha, E.M.; Guddat, L.W.; Sriram, D.

J. Comput. Aided Mol. Des.

33

357-366

763730

29739976

NADH/NADPH bi-cofactor-utilizing and thermoactive ketol-acid reductoisomerase from Sulfolobus acidocaldarius

2018

Chen, C.; Ko, T.; Lin, K.; Lin, B.; Huang, C.; Chiang, C.; Horng, J.

Sci. Rep.

8

7176

Links to other databases for (S)-2-Hydroxy-2-methyl-3-oxobutanoate

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Show Links (1 entry)

ChEBI

PubChem