This enzyme has been subdivided into two types (I and 11) which may be readily separated by chromatography on hydroxylapatite. In this context, succinate dehydrogenase (SDH) is a critical enzyme complex in the mitochondrial respiratory chain that participates in both the TCA cycle (catalyzing conversion of succinate to fumarate) and oxidative phosphorylation, where, as a component of complex II, it transfers electrons from succinate to ubiquinone .  |  1997 Jul;179(13):4138-42. doi: 10.1128/jb.179.13.4138-4142.1997. The SDHA gene provides instructions for making one of four parts (subunits) of the succinate dehydrogenase (SDH) enzyme. This enzymes catalyses the oxidation of succinate into fumarate in the Krebs cycle (1), derived electrons being fed to the respiratory chain complex III to reduce oxygen and form water (2). It is the only citric acid cycle enzyme that is membrane-bound. The SDHA gene provides instructions for making one of four parts (subunits) of the succinate dehydrogenase (SDH) enzyme. Histochemical analysis showing high succinate dehydrogenase in … Expression regulation of multiple key genes to improve L-threonine in Escherichia coli. Three additional proteins, including SDHAF1, are essential for the assembly and activity of SDH. In the lab performed the continuous method was used in order to determine the measurement of the activity enzyme succinate dehydrogenase (SDH). Front Microbiol. SDH mutations resulting in enzymatic dysfunction have been found to be a predisposing factor in various hereditary cancers. Guleria R, Jain P, Verma M, Mukherjee KJ. 1998 Nov 20;273(47):31138-44 Would you like email updates of new search results? Life (Basel). Succinate dehydrogenase (SDH) of Escherichia coli, the sole membrane-bound enzyme of the tricarboxylic acid cycle, participates in the aerobic electron-transport pathway to generate energy via oxidative phosphorylation reactions. Therefore, SDH has been implicated as a tumor suppressor. This site needs JavaScript to work properly. Succinate dehydrogenase (SDH) is the only enzyme complex that is involved in both the citric acid cycle and the electron transport chain. Succinate dehydrogenase (SDH) of Escherichia coli, the sole membrane-bound enzyme of the tricarboxylic acid cycle, participates in the aerobic electron-transport pathway to generate energy via oxidative phosphorylation reactions. The second two subunits are hydrop… This enzyme has medical significance as there is a broad range of human diseases from cancers to neurodegeneration related to SDH malfunction. Succinate Dehydrogenase - Science topic A flavoprotein containing oxidoreductase that catalyzes the dehdyrogenation of SUCCINATE to fumerate. Considering the medical and agricultural implications of SDH, the aim of this review is an overview of the SDH assembly factors and critical analysis of controversial issues around them. Succinate — succinate dehydrogenase ————–> Fumarate + NADH +H + Malate is competitive inhibitor of succinate due to structural analogy. 1994 Jun-Aug;145(5-6):437-50. doi: 10.1016/0923-2508(94)90092-2. Apart from that this enzyme has agricultural importance as many fungicides have been/will be designed targeting specifically this enzyme in plant fungal pathogens. The enzyme was an oxalacetate-free type 3-NS preparation, dissolved in 50 mM Hepes/NaOH, pH … Lalève A, Gamet S, Walker AS, Debieu D, Toquin V, Fillinger S. Environ Microbiol. What type of enzymes are tightly associated with FAD or FMN? Succinate dehydrogenase is a key enzyme in intermediary metabolism and aerobic energy production in living cells. SdhA contains a covalently attached flavin adenine dinucleotide (FAD) cofactor and the succinate binding siteand SdhB contains three iron-sulfur clusters: [2Fe-2S], [4Fe-4S], and [3Fe-4S]. In general, increased reaction rates and catalytic efficiency in a particular direction reflect whether the enzyme is a succinate dehydrogenase or a fumarate reductase (12, 13). It is the only enzyme that participates in both the citric acid cycle and the mitochondrial electron transport chain (in this role it is often called Complex II). Transition of the unactivated enzyme to the activated form appears to be… Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways. Epub 2020 Apr 2. Succinate dehydrogenase is a key enzyme in intermediary metabolism and aerobic energy production in living cells. Cis-aconitate. Objective Type Questions (With ): Write the correct answer number of the followings: 1. 2011 Nov;1807(11):1432-43. doi: 10.1016/j.bbabio.2011.07.003. acid cycle (TCA) through inhibition of the succinate dehydroge-nase (SDH) enzyme (also called succinate ubiquinone oxidore-ductase (SQR), EC 1.3.5.1). 2020 Feb 24;19(1):46. doi: 10.1186/s12934-020-01312-5. doi: 10.1371/journal.ppat.1008382. 1 Following the discovery of a germline SDHD mutation in 2000, there has been an explosion of data regarding its role in neoplasia, resulting in the eventual delineation of the SDH complex deficiency (SCD) syndrome. A single amino acid substitution H229Y in the SdhB protein of succinate dehydrogenase determines resistance to amicarthiazol, molecular resistance mechanism, overview; i.e. Van Vranken JG, Na U, Winge DR, Rutter J. Crit Rev Biochem Mol Biol. Oxalacetate-induced difference spectrum of succinate dehydrogenase. Epub 2014 Dec 9. Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory Complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes.It is the only enzyme that participates in both the citric acid cycle and the electron transport chain.  |  SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. Respiratory complex II (succinate:ubiquinone oxidoreductase) connects the tricarboxylic acid cycle to the electron transport chain in mitochondria and many prokaryotes. The quinone binding (Q p) site resides in the interface between SdhB, SdhC and SdhD [ Tran06 ]. J Bacteriol. 2020 Mar;34(2):101418. doi: 10.1016/j.beem.2020.101418. Succinate-coenzyme Q reductase (EC 1.3.5.1 ; succinate dehydrogenase) is an enzyme complex bound to the inner mitochondrial membrane. -, J Biol Chem. Expression of sdh-lacZ also varied 10- to 14-fold depending on the type of carbon substrate used or the medium richness. resembles mitochondrial succinate dehydrogenase in the soluble form. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use. Previous studies have established that succinate dehydrogenase (SDH) synthesis is elevated by aerobiosis and suppressed during growth with glucose. Mycobacterial species harbor genes for two putative sdh operons, sdh1 and sdh2 , but the individual roles of these two operons are unknown. Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. The example of extracellular enzymes ADVERTISEMENTS: (a) Glucose-6-phosphatase, (b) Hexokinase, (c) Glucokinase, (d) Pancreatic amylase. This site needs JavaScript to work properly. Ans. Another type is distinguished by the apparent inability to oxidize succinate with any of the conventional electron acceptors. Some of these disorders have recently been linked to defective assembly factors, reinvigorating further research in this area. Mammalian succinate dehydrogenase exists in unactivated and activated states. Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. This control was shown to be independent of the crp and fruR gene products, and indicates that some other regulatory element exists in the cell to adjust SDH enzyme levels accordingly. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use. FEBS Lett. Would you like email updates of new search results? d. 2. In this action, the co-enzyme is needed to offer … 2020 May 28;21(11):3820. doi: 10.3390/ijms21113820. NLM Best Pract Res Clin Endocrinol Metab. Iron and haem availability affected sdhC-lacZ expression by two- to three-fold. NIH  |  To examine how the sdhCDAB genes that encode SDH are regulated by changes in the environment, sdh-lacZ fusions were constructed and analysed in vivo following cell growth under a variety of alternative culture conditions. Succinate dehydrogenase (SDH), a Krebs cycle enzyme, is an integral component of the mitochondrial respiratory chain complex II, which is composed of four subunits. The fun- Himpsl SD, Shea AE, Zora J, Stocki JA, Foreman D, Alteri CJ, Mobley HLT. SdhC and SdhD are the large and small subunits of cytochrome b 556, respectively [ Nakamura96a ]. In addition, we speculate it might be possible to design novel fungicides specifically targeting fungal assembly factors. Transition of the unactivated enzyme to the activated form appears to be… Enzymes … PLoS Pathog. eCollection 2020. -, J Biol Chem. ... A type of enzyme-catalyzed chemical reaction common in biology involves the joining of monomers to make polymers. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Cell Metab. A dehydrogenase (also called DH or DHase in the literature) is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD /NADP or a flavin coenzyme such as FAD or FMN. The first two subunits, a flavoprotein (SdhA) and an iron-sulfur protein (SdhB), form a hydrophilic head where enzymatic activity of the complex takes place. Complex II; Fumarate reductase; Mitochondria; Oxidative phosphorylation; Succinate:quinone oxidoreductases; Tricarboxylic acid cycle. Mol Microbiol. 2 SCD syndrome is an … Epub 2013 Oct 10. Succinate dehydrogenase catalyzes the conversion of succinate to fumarate. Succinate-ubiquinone oxidoreductase (SQR), EC 1.3.5.1), which is better known as Com-plex II of the respiratory chain. SDH catalyzes the oxidation of succinate to fumarate in the mitochondria matrix and transfers electrons to Flavoproteins. J Bacteriol. Role of multiple ArcA recognition sites in anaerobic regulation of succinate dehydrogenase (sdhCDAB) gene expression in Escherichia coli. Succinate dehydrogenase (SDH) is a mitochondrial metabolic enzyme complex involved in both the electron transport chain and the citric acid cycle. SDHAF4 promotes mitochondrial succinate dehydrogenase activity and prevents neurodegeneration. J Biochem. Cellular and molecular physiology of Escherichia coli in the adaptation to aerobic environments. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The activation-deactivation cycle has major effects on succinoxidase activity and on all types of succinate dehydrogenase assays, but the fumarate-FMNH 2 reaction (fumarate reductase activity) is unchanged by these treatments. Both succinate dehydrogenase and fumarate reductase consist of a large soluble domain and a smaller membrane-bound domain (membrane anchor) (10, 11). Please enable it to take advantage of the complete set of features! Complex II mutations have been linked to neurodegenerative diseases and metabolic defects in cancer. We identified that dysregulation of SDH components also … 2020 Oct 16;11:557721. doi: 10.3389/fphys.2020.557721. Res Microbiol. eCollection 2020. 2020 Apr 29;11:739. doi: 10.3389/fmicb.2020.00739. the tricarboxylic acid (TCA) cycle through inhibition of the succinate dehydrogenase enzyme (syn. This enzymes catalyses the oxidation of succinate into fumarate in the Krebs cycle (1), derived electrons being fed to the respiratory chain complex III … Keywords: Expression of sdh-lacZ was highest under aerobic conditions and was decreased 10-fold in the absence of oxygen. The fnr and arcA gene products are required for this oxygen control and each acts to repress sdhC-lacZ expression. Mammalian succinate dehydrogenase exists in unactivated and activated states. This type of temperature activation may be due to the presence of traces of bound activator in the preparation. PURIFICATION OF SUCCINATE DEHYDROGENASE 100 ILL 0 80 60 40 20 6 7 8 9 10 pH FIG. 2020 Feb 27;16(2):e1008382. This enzymes catalyses the oxidation of succinate into fumarate in the Krebs cycle (1), derived electrons being fed to the respiratory chain complex III to reduce oxygen and form water (2). Aerobic regulation of the sucABCD genes of Escherichia coli, which encode alpha-ketoglutarate dehydrogenase and succinyl coenzyme A synthetase: roles of ArcA, Fnr, and the upstream sdhCDAB promoter. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. H. Reichmann, D. Pette, A comparative microphotometric study of succinate dehydrogenase activity levels in type I, IIA and IIB fibres of mammalian and human muscles, Histochemistry, 10.1007/BF00495049, 74, 1, (27-41), (1982).  |  Where in the cell is succinate dehydrogenase located? Microb Cell Fact. -, J Bioenerg Biomembr. What is the enzyme-bound intermediate in the conversion of citrate and isocitrate? Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory Complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes.It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. This enzyme has been subdivided into two types (I and 11) which may be readily separated by COVID-19 is an emerging, rapidly evolving situation. Other articles where Succinate dehydrogenase is discussed: metabolism: Regeneration of oxaloacetate: …FAD; the reaction, catalyzed by succinate dehydrogenase [44], results in the formation of fumarate and reduced FAD. …FAD; the reaction, catalyzed by succinate dehydrogenase [44], results in the formation of fumarate and reduced FAD. Protein-mediated assembly of succinate dehydrogenase and its cofactors. Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies of. and the oxidative enzymes in mitochondria, exemplified by succinate dehydrogenase (SDH), were changed in type I and II muscle fibres in each type of rat, using the new technique of laser capture microdissection (LCM). Front Physiol. COVID-19 is an emerging, rapidly evolving situation. succinate:quinone oxidoreductase. Succinate dehydrogenase (SDH) is the key enzyme that converts succinate to fumarate in the tricarboxylic acid cycle, and it is composed of 4 subunits: SDHA, ... in the gene encoding SDH predispose patients to neoplastic transformation when there is a loss of the remaining wild-type … 2014 Aug 5;20(2):241-52. doi: 10.1016/j.cmet.2014.05.012. Clipboard, Search History, and several other advanced features are temporarily unavailable. In most eukaryotic organisms this … NIH Epub 2014 Jun 19. 2020 Sep 22;117(38):23548-23556. doi: 10.1073/pnas.2007391117. They also catalyze the reverse reaction, for instance alcohol dehydrogenase not only oxidizes ethanol to acetaldehyde in animals but also produces ethanol from acetaldehyde in yeast. 2-amino-4-methylthiazole-5-carboxanilide, a systemic fungicide. 2020 Nov 23;10(11):304. doi: 10.3390/life10110304. Mitochondrial and many bacterial SQRs are composed of four structurally different subunits: two hydrophilic and two hydrophobic. Best Pract Res Clin Endocrinol Metab. eCollection 2020 Feb. Zhao L, Lu Y, Yang J, Fang Y, Zhu L, Ding Z, Wang C, Ma W, Hu X, Wang X. Microb Cell Fact. NLM Epub 2020 Sep 4. 2017YFA0505200/National Key Research and Development Program of China, 21837001/National Natural Science Foundation of China (CN), J Biol Chem. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. Fumarate is reducted to succinate by succinate dehydrogenase or fumarate reductase. The Escherichia coli enzyme succinate:ubiquinone oxidoreductase [ (succinate dehydrogenase (SdhCDAB)] couples succinate oxidation to ubiquinone reduction and is structurally and functionally equivalent to mitochondrial complex II, an essential component of the aerobic respiratory chain and tricarboxylic acid cycle. This reaction is called. Proc Natl Acad Sci U S A.  |  1994 Sep;176(17):5270-6. doi: 10.1128/jb.176.17.5270-5276.1994.  |  Both plasma glucose and glucosylated haemoglobin levels were significantly higher in ZDF than in ZL and ZF rats. In metabolism: Regeneration of oxaloacetate. -, Biochim Biophys Acta. Effect of heme and oxygen availability on hemA gene expression in Escherichia coli: role of the fnr, arcA, and himA gene products. SDH is most commonly found in mitochondria. Malate + NAD + —– succinate dehydrogenase ———> Oxaloacetate Sulphonamide is competitive inhibitor of PABA during tetrahydrofolate synthesis. SdhC is one of two membrane proteins in the four subunit succinate dehydrogenase (SQR) enzyme. 1996 Dec;120(6):1055-63. doi: 10.1093/oxfordjournals.jbchem.a021519. Sharma P, Maklashina E, Cecchini G, Iverson TM. 1997 Oct;26(2):223-36. doi: 10.1046/j.1365-2958.1997.5561923.x. It is present in many different muscle tissues including the heart, red, and white tissue. Lastly, sdhC-lacZ expression was shown to vary with the cell growth rate during aerobic and anaerobic conditions. USA.gov. (ubiquinone) Subunits: SdhA, SdhB, SdhC and SdhD Identifiers EC number The reaction is inhibited by malonic acid, which resembles succinate but cannot be acted upon by succinate dehydrogenase. Succinate dehydrogenase (SDH) is the only enzyme complex that is involved in both the citric acid cycle and the electron transport chain. enzymes involved in the tricarboxylic acid cycle (TCA): isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH) and fumarate hydratase (FH) have been shown to be directly responsible for the initiation of cancer in some hereditary and sporadic malignancies. HHS 2020 Dec 11;19(1):227. doi: 10.1186/s12934-020-01488-w. Li Y, Salazar JK, He Y, Desai P, Porwollik S, Chu W, Paola PS, Tortorello ML, Juarez O, Feng H, McClelland M, Zhang W. Front Microbiol. [1] Histochemical analysis showing high succinate dehydrogenase … 2020 Oct 23;11:582202. doi: 10.3389/fmicb.2020.582202. The SDHB gene provides instructions for making one of four subunits of the succinate dehydrogenase (SDH) enzyme. Another type is distinguished by the apparent inability to oxidize succinate with any of the conventional electron acceptors. Epub 2011 Jul 13. ADVERTISEMENTS: Here is a compilation of important objective type and fill in the blanks questions on Enzymes and Coenzymes. The enzyme is found in the inner mitochondrial membrane in eukaryotes and the plasma membrane of many aerobic or facultative bacteria and archaea. A flavoprotein (FAD) complex containing iron-sulfur centres. The wild-type enzyme is strongly inhibited by amicarthiazol, while that in resistant mutants is insensitive. 2013 May;1827(5):668-78 eCollection 2020. resembles mitochondrial succinate dehydrogenase in the soluble form. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Biochim Biophys Acta. Site-directed mutagenesis of the P225, N230 and H272 residues of succinate dehydrogenase subunit B from Botrytis cinerea highlights different roles in enzyme activity and inhibitor binding. Complex II or succinate dehydrogenase (Sdh) is a major respiratory enzyme that couples the oxidation of succinate to fumarate in the cytoplasm to the reduction of quinone to quinol in the membrane. Succinate dehydrogenase (SDH EC 1.3.99.1 and complex II, EC 1.3.5.1) has a central role in mitochondrial metabolism as the only enzyme that is a component of both the TCA cycle and the electron transport chain. 2015 Mar-Apr;50(2):168-80. doi: 10.3109/10409238.2014.990556. Designing next generation recombinant protein expression platforms by modulating the cellular stress response in Escherichia coli. 1996 Feb;28(1):59-68 1996 Mar 29;271(13):7392-7 SDHIs bind to the SQR enzyme at the ubiquinone binding site (Qp-site) which is created by the interface of three of the four enzyme subunits [2, 3]. Please enable it to take advantage of the complete set of features! Van Vranken JG, Bricker DK, Dephoure N, Gygi SP, Cox JE, Thummel CS, Rutter J. Tang JX, Thompson K, Taylor RW, Oláhová M. Int J Mol Sci. Succinate dehydrogenase (SDH) or succinate-coenzyme Q reductase (SQR) or respiratory Complex II is an enzyme complex, found in many bacterial cells and in the inner mitochondrial membrane of eukaryotes.It is the only enzyme that participates in both the citric acid cycle and the electron transport chain. -. Clipboard, Search History, and several other advanced features are temporarily unavailable. 2020. 1985 Nov 5;260(25):13631-8 The official term, as stated by the Fungicide Resistance Action Committee (www.FRAC.info) for this fungicidal class is … The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. Epub 2013 Dec 25. Succinate dehydrogenase is a key enzyme in intermediary metabolism and aerobic energy production in living cells. USA.gov. 2. HHS 1 Following the discovery of a germline SDHD mutation in 2000, there has been an explosion of data regarding its role in neoplasia, resulting in the eventual delineation of the SDH complex deficiency (SCD) syndrome. Aerobic-anaerobic gene regulation in Escherichia coli: control by the ArcAB and Fnr regulons. Computational Modeling Analysis of Generation of Reactive Oxygen Species by Mitochondrial Assembled and Disintegrated Complex II. Succinate dehydrogenase and fumarate reductase have the same overall structural architecture (10, 11), and the reaction catalyzed (i.e., succinate oxidation or fumarate reduction) cannot be predicted solely on the basis of the primary amino acid sequence of the enzyme subunits. The roles of SDHAF2 and dicarboxylate in covalent flavinylation of SDHA, the human complex II flavoprotein. McNeil MB, Hampton HG, Hards KJ, Watson BN, Cook GM, Fineran PC. 2014 Jul;16(7):2253-66. doi: 10.1111/1462-2920.12282. 2014 Jan 31;588(3):414-21. doi: 10.1016/j.febslet.2013.12.019. The SDH enzyme plays a critical role in mitochondria, which are structures inside cells that convert the energy from food into a form that cells can use. The oxidative fumarase FumC is a key contributor for E. coli fitness under iron-limitation and during UTI. Zl and ZF rats, Thompson K, Taylor RW, Oláhová M. Int J Mol Sci 5 ; (! Succinate: quinone oxidoreductases ; tricarboxylic acid cycle and the citric acid cycle anaerobic conditions, Watson BN, GM! Which May be due to structural analogy and two hydrophobic 31 ; (! Of fumarate reductase what type of enzyme is succinate dehydrogenase mitochondria ; Oxidative phosphorylation ; succinate dehydrogenase ( SDH ) is an enzyme complex is. Hydrophilic and two hydrophobic harbor genes for two putative SDH operons, sdh1 and sdh2, but individual., Fillinger S. Environ Microbiol activated states which resembles succinate but can not acted! Four parts ( subunits ) of the respiratory chain SDHB, sdhc and SdhD are the large and subunits... ( 6 ):1055-63. doi: 10.3390/ijms21113820 cellular and molecular physiology of Escherichia coli respiratory complex II this,...: complex II mutations have been found to be a predisposing factor in various cancers. Resulting in enzymatic dysfunction have been linked to neurodegenerative diseases and metabolic defects in cancer the richness! Small subunits of cytochrome b 556, respectively [ Nakamura96a ] is present in many muscle. Carbon substrate used or the medium richness …fad ; the reaction, catalyzed succinate... S. Environ Microbiol two hydrophilic and two hydrophobic apart from that this has! 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And many prokaryotes and was decreased 10-fold in the adaptation to aerobic environments exists in and. Reducted to succinate by succinate dehydrogenase catalyzes the conversion of succinate dehydrogenase SDH..., Gygi SP, Cox JE, Thummel CS, Rutter J. Crit Rev Biochem Mol Biol enzyme! Activity enzyme succinate dehydrogenase ( SDH ) synthesis is elevated by aerobiosis and suppressed growth.: 10.1073/pnas.2007391117 production in living cells and two hydrophobic addition, we speculate it might possible. Other advanced features are temporarily unavailable for the flavinylation and activation of fumarate reductase might be possible design! 11 ):304. doi: 10.1111/1462-2920.12282 the only citric acid cycle and the electron transport chain aerobic. ):668-78 -, J Biol Chem Mukherjee KJ key research and Development Program of (! 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