|Gene:||yqhD||Accession Numbers: G7564 (EcoCyc), b3011, ECK3003|
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 [Zhang05b, Wang07c]. The use of YqhD in the industrial production of 1,3-propanediol by engineered E. coli has been reviewed in [Nakamura03a]. 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 [Lee10a], and contains increased levels of reactive aldehydes that are generated during lipid peroxidation [Perez08]. Conversely, yqhD deletion leads to increased furfural tolerance [Wang13a].
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 [Lee10a].
Gene Citations: [Turner11]
|Map Position: [3,153,377 -> 3,154,540] (67.97 centisomes, 245°)||Length: 1164 bp / 387 aa|
Molecular Weight of Polypeptide: 42.097 kD (from nucleotide sequence), 43.0 kD (experimental) [Zhang05b ]
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
In Paralogous Gene Group: 266 (7 members)
Instance reaction of [an aldehyde + NADP+ + H2O → a carboxylate + NADPH + 2 H+] (188.8.131.52):
Instance reactions of [an alcohol + NADP+ = an aldehyde + NADPH + H+] (184.108.40.206):
|Biological Process:||GO:0000302 - response to reactive oxygen species
GO:0051143 - propanediol metabolic process [Wang07c]
GO:0055114 - oxidation-reduction process [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0004022 - alcohol dehydrogenase (NAD) activity
GO:0008106 - alcohol dehydrogenase (NADP+) activity [Sulzenbacher04]
GO:0008270 - zinc ion binding [Sulzenbacher04]
GO:0033721 - aldehyde dehydrogenase (NADP+) activity [Perez08]
GO:0016491 - oxidoreductase activity [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding [UniProtGOA11a, GOA01a]
|Cellular Component:||GO:0005829 - cytosol [DiazMejia09, Ishihama08, LopezCampistrou05]|
|MultiFun Terms:||cell processes → protection|
|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]|
Enzymatic reaction of: aldehyde reductase
Synonyms: aldehyde reductase
EC Number: 220.127.116.11
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.
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].
T(opt) (reverse direction): 50 °C [Pick13]
Enzymatic reaction of: aldehyde dehydrogenase (NADPH-dependent aldehyde reductase)
EC Number: 18.104.22.168
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.-
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.
|Feature Class||Location||Attached Group||Citations||Comment|
|Nucleotide-Phosphate-Binding-Region||38 -> 40||NADP+|
|Nucleotide-Phosphate-Binding-Region||93 -> 99||NADP+|
|Nucleotide-Phosphate-Binding-Region||179 -> 182||NADP+|
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
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
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
Lee10a: 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
Lee12a: 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
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
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
Tang09a: 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
Wang07c: 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
Wang13a: 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
Zhang05b: 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
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