L-lysine e-aminotransferase

Figure 13.21 L-Lysine e-aminotransferase reactions to Omapatrilate precursors (Patel, 2000).

In the biotransformation process with L-lysine e-aminotransferase in recombinant E. coli cells, a reaction yield of 65-70% mol/mol was obtained for conversion of BMS-201391-01 (Cbz protecting group) to BMS-199541-01 depending upon the reaction conditions used in the process. Similar molar yields were obtained with phenylacetyl- or phenoxyacetyl-protected analogs of BMS-201391-01. Even Na-pro-tected L-Met/L-Homocys-L-Lys dipeptides served as substrates, as did N-e-Cbz- or Boc-protected L-lysines. 

L. W. Parker, and J. J. Venit, Biocatalytic preparation of a chiral synthon for a vasopeptidase inhibitor enzymatic conversion of N2-[N-phenylmethoxy)carbo-nyl] L-homocysteinyl]- l-lysine (1,1 J-disulfide to 4S-(4/,71,10aJ)]-l-octahydro-5-oxo-4-[phenylmethoxy)carbonyl]amino]-7H-pyrido-[2,l-b][l,3]thiazepine-7-carboxylic add methyl ester by a novel l -lysine e-aminotransferase, Enzyme Microb. Technd. 2000, 27, 376-389. 

Synthesis of an Omapatriiat Building Block with L-Lysine e-Aminotransferase... 

In the biotransformation process to BMS-199541-01, yields of65-70 mole-% were achieved without recycling of the L-glutamate resulting from the reduction of a-ketoglutarate yields were substantially lower. L-Lysine E-aminotransferase also catalyzes the oxidation of N-a-protected L-lysines as well as L-lysine peptides such as N-protected L-met-L-lys. 

L-Lysine-e-aminotransferase from Sphingomonas paucimobilis or rec E. coli... 

This enzyme [EC 2.6.1.36], also called lysine e-aminotransferase, catalyzes the pyridoxal-phosphate-depen-dent reaction of L-lysine with a-ketoglutarate (or, 2-ox-oglutarate) to produce 2-aminoadipate 6-semialdehyde... 

MB Tobin, S Kovacevic, K Madduri, JA Hoskins, PL Skatrud, LC Vining, C Stut-tard, JR Miller. Localization of the lysine e-aminotransferase (lat) and 5-(L-aminoadipyl)-L-(cysteinyl)-D-valine synthetase (pcbAB) genes from Streptomyces clavuligerus and production of lysine-e-aminotransferase in Escherichia coli. J Bacteriol 173 6223-6229, 1991. 

Kem BA, Henditn D, Inamine E. l-Lysine C aminotransferase involved in cephamycin C synthesis in Strepcomyces loctamdurans. Antimicrob Agents Chemother 1980 17 676 85. 

L-Lysine- -dehydrogenase (EC 1.4.1.15), an enzyme specific for the 4-pro-R hydrogen of NADPH (270), has been incubated with (2S,6R)- and (2S, 6S)-[6- H,]lysines 257a, Hc- = H, and 257a, H = H, respectively, and shown to be converted to A -piperideine-6-carboxyIate 265 with loss of the 6-pro-R hydrogen (271). The stereochemistry is very different from that exhibited by the e-aminotransferase, but it is in keeping with that of a D-amino acid dehydrogenase. 

The potential of biotransformations with genetically modified microorganisms can be illustrated by the following example, where the chain of added-value to amino acid products is also recognisable The Mercian Company (Japan) uses a recombinant E. coli strain to prepare (S)-piperidine-2-car-boxylic acid from (L)-lysine. In this strain, the (L)-lysine-permease transport system is overexpressed, so that in this pathway lysine is produced efficiently in the cells. The bacteria possess additionally a (L)-lysine-aminotransferase from Flavobacterium lutescens, which brings about the deamination of lysine. The thus generated aldehyde is in equilibrium with its intramolecular imine, which, in presence of the E. co/i-specific pyrroline-5-carboxylate reductase, is reduced with NADPH to (S)-piperidine-2-carboxylic acid. The turnover... 

Chan-Huot, M., Dos, A., Zander, R., Sharif, S., Tolstoy, P.M., Compton, S., Fogle, E., Toney, M.D., Shenderovich, I.G., Denisov, G.S., and Limbach, H.H. (2013) NMR studies of protonation and hydrogen bond states of internal aldimines of pyridoxal 5 -phosphate acid-base in alanine racemase, aspartate aminotransferase and poly-L-lysine. / Am. Chem. Soc., 135, 18160-18175,... 

A number of studies have shown that natural metabolites can inhibit transamination. With a partially purified mung bean preparation which could use lysine, methionine, or aromatic amino acids as amino donors, it was found that the aliphatic substrates (e.g., lysine and methionine) inhibited the transamination of phenylalanine. The extent of this inhibition was related to their effectiveness as substrates, suggesting that they competed with phenylalanine (Gamborg, 1965). Using the highly purified but multispecific aromatic amino acid (and aspartate) aminotransferase from bush bean. Forest and Wightman (1973) demonstrated that 40 mM aspartate inhibited transamination of L-phenylalanine (40 mM) by 85%. Further experiments showed that elevated concentrations of phenylalanine reduced the inhibition by aspartate double-reciprocal plots indicated competitive inhibition. These... 

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