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Escherichia coli K-12 substr. MG1655 Enzyme: NADPH-dependent aldehyde reductase

Gene: yqhD Accession Numbers: G7564 (EcoCyc), b3011, ECK3003

Regulation Summary Diagram: ?

Subunit composition of NADPH-dependent aldehyde reductase = [YqhD]2
         NADPH-dependent aldehyde reductase = YqhD

YqhD is an NADP-dependent aldehyde dehydrogenase which may be part of a glutathione-independent response to lipid peroxidation [Perez08].

[Sulzenbacher04] report that various alcohols, aldehydes, amino acids, sugars and α-hydroxy acids were tested as substrates for YqhD. The purified protein only showed NADP-dependent alcohol dehydrogenase activity, with a preference for alcohols longer than C(3), but with Km values in the millimolar range, suggesting that they are not the physiological substrates [Sulzenbacher04]. In contrast, [Perez08, Atsumi10] report that YqhD does exhibit short-chain aldehyde reductase activity with substrates such as propanaldehyde, acetaldehyde, and butanaldehyde, as well as acrolein and malondialdehyde. In a metabolically engineered strain, phenylacetaldehyde and 4-hydroxyphenylacetaldehyde are reduced to 2-phenylethanol and 2-(4-hydroxyphenyl)ethanol by the endogenous aldehyde reductases YqhD, YjgB, and YahK [Koma12].

Overexpression of YqhD increases 1,3-propanediol oxidoreductase activity of the cell [Zhang05g, Wang07g]. The use of YqhD in the industrial production of 1,3-propanediol by engineered E. coli has been reviewed in [Nakamura03]. YqhD activity contributes to he production of isobutanol as well [Atsumi10]. Mutation of yqhD enables production of butanol by an engineered one-turn reversal of the β-oxidation cycle [Dellomonaco11].

YqhD has furfural reductase activity, which appears to cause growth inhibition due to depletion of NADPH in metabolically engineered strains that produce alcohol from lignocellulosic biomass [Miller09, Miller09a].

The crystal structure of YqhD has been solved at 2 Å resolution. YqhD is an asymmetric dimer of dimers, and the active site contains a Zn2+ ion. The NADPH cofactor is modified by hydroxyl groups at positions 5 and 6 in the nicotinamide ring [Sulzenbacher04].

Overexpression of yqhD leads to increased resistance to reactive oxygen-generating compounds such as hydrogen peroxide, paraquat, chromate and potassium tellurite. A yqhD deletion mutant shows increased sensitivity to these compounds [Perez08] and to glyoxal [Lee10c], and contains increased levels of reactive aldehydes that are generated during lipid peroxidation [Perez08]. Conversely, yqhD deletion leads to increased furfural tolerance [Wang13b].

Transcription of yqhD is induced by exposure to conditions of lipid peroxidation [Perez08]. Various microarray experiments showed induction of yqhD upon cold shock [Phadtare04], nutrient limitation [Hua04] and n-butanol stress [Rutherford10]. Transcription is activated by YqhC and enhanced by addition of glyoxal [Lee10c].

Review: [Jarboe11]

Citations: [Lee12e, Zhu13]

Gene Citations: [Turner11]

Locations: cytosol

Map Position: [3,153,377 -> 3,154,540] (67.97 centisomes)
Length: 1164 bp / 387 aa

Molecular Weight of Polypeptide: 42.097 kD (from nucleotide sequence), 43.0 kD (experimental) [Zhang05g ]

Unification Links: ASAP:ABE-0009888 , DIP:DIP-12870N , EchoBASE:EB2834 , EcoGene:EG13014 , EcoliWiki:b3011 , ModBase:Q46856 , OU-Microarray:b3011 , PortEco:yqhD , Pride:Q46856 , Protein Model Portal:Q46856 , RefSeq:NP_417484 , RegulonDB:G7564 , SMR:Q46856 , String:511145.b3011 , Swiss-Model:Q46856 , UniProt:Q46856

Relationship Links: InterPro:IN-FAMILY:IPR001670 , InterPro:IN-FAMILY:IPR018211 , PDB:Structure:1OJ7 , Pfam:IN-FAMILY:PF00465 , Prosite:IN-FAMILY:PS00060 , Prosite:IN-FAMILY:PS00913

In Paralogous Gene Group: 266 (7 members)

Gene-Reaction Schematic: ?

Instance reaction of [an aldehyde + NADP+ + H2O → a carboxylate + NADPH + 2 H+] (
i3: acetaldehyde + NADP+ + H2O → acetate + NADPH + 2 H+ (

Instance reactions of [an alcohol + NADP+ = an aldehyde + NADPH + H+] (
i1: (S)-propane-1,2-diol + NADP+ = (S)-lactaldehyde + NADPH + H+ (1.1.1.-)

i2: (R)-propane-1,2-diol + NADP+ = (R)-lactaldehyde + NADPH + H+ (1.1.1.-)

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0000302 - response to reactive oxygen species Inferred from experiment [Perez08]
GO:0051143 - propanediol metabolic process Author statement [Wang07g]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0004022 - alcohol dehydrogenase (NAD) activity Inferred from experiment [Sulzenbacher04]
GO:0008106 - alcohol dehydrogenase (NADP+) activity Inferred from experiment [Sulzenbacher04]
GO:0008270 - zinc ion binding Inferred from experiment [Sulzenbacher04]
GO:0033721 - aldehyde dehydrogenase (NADP+) activity Inferred from experiment [Perez08]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11, GOA01]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11, GOA01]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: cell processes protection

Essentiality data for yqhD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Created 27-Feb-2008 by Keseler I , SRI International
Last-Curated ? 13-Nov-2013 by Keseler I , SRI International

Enzymatic reaction of: aldehyde reductase

Synonyms: aldehyde reductase

EC Number:

an alcohol + NADP+ <=> an aldehyde + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Alternative Substrates for an aldehyde: glycolaldehyde [Liu13a ] , butanal [Pick13 ] , glyoxal [Lee10c ] , isobutanal [Atsumi10 ] , acetaldehyde [Atsumi10 ] , furfural [Miller09 ]

Km values were measured for various substrates and range between 6 mM for benzyl alcohol and 36 mM for 1-butanol. Km for NADP ranges between 17 µM with 1-octanol and 100 µM with benzyl alcohol as the substrate [Sulzenbacher04]. The Km for acetaldehyde and isobutyraldehyde is 27.6 mM and 1.8 mM, respectively [Atsumi10]; the Km for furfural is 9 mM [Miller09].

Cofactors or Prosthetic Groups: Zn2+ [Sulzenbacher04]

Kinetic Parameters:

Km (μM)

T(opt) (reverse direction): 50 °C [Pick13]

Enzymatic reaction of: aldehyde dehydrogenase (NADPH-dependent aldehyde reductase)

EC Number:

an aldehyde + NADP+ + H2O <=> a carboxylate + NADPH + 2 H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.

Km values were measured for various substrates and range between 670 µM for butanaldehyde and 28 mM for acetaldehyde [Perez08].

Enzymatic reaction of: 1,3-propanediol dehydrogenase (NADPH-dependent aldehyde reductase)

EC Number: 1.1.1.-

1,3-propanediol + NADP+ <=> 3-hydroxypropionaldehyde + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.

Note: The enzyme may catalyze this reaction in vitro, but this reaction is not considered to be physiologically relevant.

Sequence Features

Feature Class Location Citations Comment
Nucleotide-Phosphate-Binding-Region 38 -> 40
UniProt: NADP;
Nucleotide-Phosphate-Binding-Region 93 -> 99
UniProt: NADP;
Amino-Acid-Sites-That-Bind 138
UniProt: NADP;
Amino-Acid-Sites-That-Bind 147
UniProt: NADP;
Amino-Acid-Sites-That-Bind 160
UniProt: NADP;
Nucleotide-Phosphate-Binding-Region 179 -> 182
UniProt: NADP;
Metal-Binding-Site 194
UniProt: Zinc; catalytic;
Metal-Binding-Site 198
UniProt: Zinc; catalytic;
Metal-Binding-Site 267
UniProt: Zinc; catalytic;
Metal-Binding-Site 281
UniProt: Zinc; catalytic;

Gene Local Context (not to scale): ?

Transcription Units:


Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


Atsumi10: Atsumi S, Wu TY, Eckl EM, Hawkins SD, Buelter T, Liao JC (2010). "Engineering the isobutanol biosynthetic pathway in Escherichia coli by comparison of three aldehyde reductase/alcohol dehydrogenase genes." Appl Microbiol Biotechnol 85(3);651-7. PMID: 19609521

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Dellomonaco11: Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011). "Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals." Nature 476(7360);355-9. PMID: 21832992

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hua04: Hua Q, Yang C, Oshima T, Mori H, Shimizu K (2004). "Analysis of gene expression in Escherichia coli in response to changes of growth-limiting nutrient in chemostat cultures." Appl Environ Microbiol 70(4);2354-66. PMID: 15066832

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jarboe11: Jarboe LR (2011). "YqhD: a broad-substrate range aldehyde reductase with various applications in production of biorenewable fuels and chemicals." Appl Microbiol Biotechnol 89(2);249-57. PMID: 20924577

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Koma12: Koma D, Yamanaka H, Moriyoshi K, Ohmoto T, Sakai K (2012). "Production of aromatic compounds by metabolically engineered Escherichia coli with an expanded shikimate pathway." Appl Environ Microbiol 78(17);6203-16. PMID: 22752168

Lee10c: Lee C, Kim I, Lee J, Lee KL, Min B, Park C (2010). "Transcriptional activation of YqhD aldehyde reductase by YqhC protein and its implication in glyoxal metabolism of Escherichia coli K-12." J Bacteriol 192(16):4205-14. PMID: 20543070

Lee12e: Lee C, Park C (2012). "Development of a suicidal vector-cloning system based on butanal susceptibility due to an expression of YqhD aldehyde reductase." J Microbiol 50(2);249-55. PMID: 22538653

Liu13a: Liu H, Ramos KR, Valdehuesa KN, Nisola GM, Lee WK, Chung WJ (2013). "Biosynthesis of ethylene glycol in Escherichia coli." Appl Microbiol Biotechnol 97(8);3409-17. PMID: 23233208

LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532

Miller09: Miller EN, Jarboe LR, Yomano LP, York SW, Shanmugam KT, Ingram LO (2009). "Silencing of NADPH-dependent oxidoreductase genes (yqhD and dkgA) in furfural-resistant ethanologenic Escherichia coli." Appl Environ Microbiol 75(13);4315-23. PMID: 19429550

Miller09a: Miller EN, Jarboe LR, Turner PC, Pharkya P, Yomano LP, York SW, Nunn D, Shanmugam KT, Ingram LO (2009). "Furfural inhibits growth by limiting sulfur assimilation in ethanologenic Escherichia coli strain LY180." Appl Environ Microbiol 75(19);6132-41. PMID: 19684179

Nakamura03: Nakamura CE, Whited GM (2003). "Metabolic engineering for the microbial production of 1,3-propanediol." Curr Opin Biotechnol 14(5);454-9. PMID: 14580573

Perez08: Perez JM, Arenas FA, Pradenas GA, Sandoval JM, Vasquez CC (2008). "Escherichia coli YqhD exhibits aldehyde reductase activity and protects from the harmful effect of lipid peroxidation-derived aldehydes." J Biol Chem 283(12):7346-53. PMID: 18211903

Phadtare04: Phadtare S, Inouye M (2004). "Genome-wide transcriptional analysis of the cold shock response in wild-type and cold-sensitive, quadruple-csp-deletion strains of Escherichia coli." J Bacteriol 186(20);7007-14. PMID: 15466053

Pick13: Pick A, Ruhmann B, Schmid J, Sieber V (2013). "Novel CAD-like enzymes from Escherichia coli K-12 as additional tools in chemical production." Appl Microbiol Biotechnol 97(13);5815-24. PMID: 23093176

Rutherford10: Rutherford BJ, Dahl RH, Price RE, Szmidt HL, Benke PI, Mukhopadhyay A, Keasling JD (2010). "Functional genomic study of exogenous n-butanol stress in Escherichia coli." Appl Environ Microbiol 76(6);1935-45. PMID: 20118358

Sulzenbacher04: Sulzenbacher G, Alvarez K, Van Den Heuvel RH, Versluis C, Spinelli S, Campanacci V, Valencia C, Cambillau C, Eklund H, Tegoni M (2004). "Crystal structure of E.coli alcohol dehydrogenase YqhD: evidence of a covalently modified NADP coenzyme." J Mol Biol 342(2);489-502. PMID: 15327949

Tang09: Tang X, Tan Y, Zhu H, Zhao K, Shen W (2009). "Microbial conversion of glycerol to 1,3-propanediol by an engineered strain of Escherichia coli." Appl Environ Microbiol 75(6);1628-34. PMID: 19139229

Turner11: Turner PC, Miller EN, Jarboe LR, Baggett CL, Shanmugam KT, Ingram LO (2011). "YqhC regulates transcription of the adjacent Escherichia coli genes yqhD and dkgA that are involved in furfural tolerance." J Ind Microbiol Biotechnol 38(3);431-9. PMID: 20676725

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wang07g: Wang F, Qu H, Zhang D, Tian P, Tan T (2007). "Production of 1,3-propanediol from glycerol by recombinant E. coli using incompatible plasmids system." Mol Biotechnol 37(2);112-9. PMID: 17914171

Wang13b: Wang X, Yomano LP, Lee JY, York SW, Zheng H, Mullinnix MT, Shanmugam KT, Ingram LO (2013). "Engineering furfural tolerance in Escherichia coli improves the fermentation of lignocellulosic sugars into renewable chemicals." Proc Natl Acad Sci U S A 110(10);4021-6. PMID: 23431191

Zhang05g: Zhang XM, Tang XM, Zhuge B, Shen W, Rao ZM, Fang HY, Zhuge J (2005). "[Construction of novel recombinant Escherichia coli capable of producing 1,3-propanediol]." Sheng Wu Gong Cheng Xue Bao 21(5);743-7. PMID: 16285515

Zhu13: Zhu H, Yi X, Liu Y, Hu H, Wood TK, Zhang X (2013). "Production of acetol from glycerol using engineered Escherichia coli." Bioresour Technol 149;238-43. PMID: 24113547

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Jan 28, 2015, BIOCYC13A.