Aspartokinase and

Zhang, W.W. Jiang, W.H. Zhao, G.P. Yang, Y.L. Chiao, J.S. Expression in Escherichia coli, purification and kinetic analysis of the aspartokinase and aspartate semialdehyde dehydrogenase from the rifamycin SV-producing Amycolatopsis mediterranei U32. Appl. Microbiol. Biotechnol., 54, 52-58 (2000)... 

The Aspartokinases and Homoserine Dehydrogenases of Escherichia coli Georges N. Cohen... 

In E. coli there are three aspartokinases I (coded by thrA), II (coded by met L), and III (coded by lysC) and two homoserine dehydrogenases I and II that are inhibited or repressed by only one or two amino acids of the aspartate family which ensures that pathway is not shut down with the excess of one product. Each amino acid regulates the first enzyme in its branch to maintain the proper ratio of the amino acids. In Corynebacterium, the regulation is much simpler with only one aspartokinase and here the amino acid biosynthesis is controlled by the synergistic action of the end products. 

S Additional information <9, 15, 17, 18, 21, 24, 30, 33, 35> (<18> activity is regulated by light [28] <30> D-aspartate, L-glutamate and -alanine are inactive as substitutes for L-aspartate in the forward reaction, in the reverse reaction ADP cannot be replaced by AMP, UDP, GDP or IDP [1] <17> aspartokinase III, o-isomers of the derivatives of aspartic acid, including D-aspartate cr-benzyl ester and o-aspartate /)-hydroxamate are not substrates regardless of whether the a- or the -carboxyl group is derivatized, L-cysteine sulfinate and 2-methyl-DL-aspartate are no substrates... 

Kuramitsu, H.K. Yoshimura, S. Catalytic and regulatory properties of meso-diaminopimelate-sensitive aspartokinase from Bacillus stearother-mophilus. ArcL Biochem. Biophys., 147, 683-691 (1971)... 

Starnes, W.L. Munk, P. Maul, S.B. Cunningham, G.N. Cox, D.J. Shive, W. Threonine-sensitive aspartokinase-homoserine dehydrogenase complex, amino acid composition, molecular weight, and subunit composition of the complex. Biochemistry, 11, 677-687 (1972)... 

Veron, M. Falcoz-Kelly E Cohen, G.N. The threonine-sensitive homoserine dehydrogenase and aspartokinase activities of Escherichia coli K12. The two catalytic activities are carried by two independent regions of the polypeptide chain. Eur. J. Biochem., 28, 520-527 (1972)... 

Biswas, C. Paulus, H. Multivalent feedback inhibition of aspartokinase in Bacillus polymyxa. IV. Arrangement and function of the subunits. J. Biol. Chem., 248, 2894-2900 (1973)... 

Dawson Funkhouser, J. Abraham, A. Smith, V.A. Smith W.G. Kinetic and molecular properties of lysine-sensitive aspartokinase. Factors influencing the lysine-mediated association reaction and their relationship to the cooperativity of lysine inhibition. J. Biol. Chem., 249, 5478-5484 (1974)... 

Hitchcock, M.J.M. Hodgson, B. Lysine- and lysine-plus-threonine-inhibi-table aspartokinases in Bacillus brevis. Biochim. Biophys. Acta, 445, 350-363 (1976)... 

Saiki, T. Yamazumi, K. Arima, K. Aspartokinase of an extreme thermo-phile Thermus flavus partial purification and some properties. Agric. Biol. Chem., 41, 1651-1655 (1977)... 

Keng, Y.-F. Viola, R.E. Specificity of aspartokinase III from Escherichia coli and an examination of important catalytic residues. Arch. Biochem. Biophys., 335, 73-81 (1996)... 

Hernando-Rico, V. Martin, J.F. Santamarta, L Liras, P. Structure of the ask-asd operon and formation of aspartokinase subunits in the cephamycin... 

King, N.D. O Brian, M.R. Evidence for direct interaction between enzyme INtr and aspartokinase to regulate bacterial oligopeptide transport. J. Biol. Chem., 276, 21311-21316 (2001)... 

In many cases the amino acid pathway branches so that two or more amino acids are formed. Aspartate is the precursor of four other amino acids found in proteins Isoleucine, threonine, methionine, and lysine (see fig. 21.2). The first step in this overall pathway entails the conversion of aspartate to /3-aspartyl-phosphate by aspartokinase. One might imagine that all four of the amino acid end products of this pathway would act together to inhibit this enzyme. However, in E. coli a different solution has been found. In this bacterium there are three aspartokinases which appear to be parts of different multienzyme complexes leading to threonine and leucine for aspartokinase I, methionine for aspartokinase II and lysine for aspartokinase III. As might be expected threonine and isoleucine inhibit aspartokinase I,... 

S-(2-Aminoethyl)-L-cysteine (AEC), H2N-CH2-CH2-S-CH2-CH(NH2)-COOH, a lysine analog, acts as a false feedback inhibitor on aspartokinase, which produces aspartylphosphate from aspartate. The inhibitor simulates, for aspartokinase, the absence of lysine and threonine, and as a consequence the AEC insensitive mutant is no longer inhibited by lysine and threonine. The result was a yield increase from 0 to 16 g L 1. 

Overproduction of E (isoleucine) inhibits enzyme E6 (threonine deaminase), and the consequent rise of D (threonine) reduces the rate of production of C (homoserine) via enzyme E3 (homoserine dehydrogenase). The concentration of B (aspartate semialdehyde) rises, and this in turn inhibits Ej (aspartokinase). It is therefore obvious why the control system is called a negative feedback network, or sequential feedback system. 

Ogawa-Miyata Y, Kojima H, Sano K (2001) Mutation analysis of the feedback inhibition site of aspartokinase III of Escherichia coli K-12 and its use in L-threonine production. Biosci Biotech Biochem 65 1149-1154... 

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