Norvaline pathway

Butanol Production via Norvaline Pathway Besides isobutanol it is possible to use the amino acid pathways to produce 1-butanol and 1-propanol that share a conmiOTi precursor— threonine. 

The question of the stability of the biomolecules is a vital one. Could they really have survived the tremendous energies which would have been set free (in the form of shock waves and/or heat) on the impact of a meteorite Blank et al. (2000) developed a special technique to try and answer this question. They used an 80-mm cannon to produce the shock waves the shocked solution contained the two amino acids lysine and norvaline, which had been found in the Murchison meteorite. Small amounts of the amino acids survived the bombardment , lysine seeming to be a little more robust. In other experiments, the amino acids aminobutyric acid, proline and phenylalanine were subjected to shock waves the first of the three was most stable, the last the most reactive. The products included amino acid dimers as well as cyclic diketopiperazine. The kinetic behaviour of the amino acids differs pressure seems to have a greater effect on the reaction pathway than temperature. As had been recognized earlier, the effect of pressure would have slowed down certain decomposition reactions, such as pyrolysis and decarboxylation (Blank et al., 2001). 

Fig. 4a. Pathways of hydroxamic acid syntheses of siderophores containing Ns-hydroxyornithine building blocks, a) Starts with e-nitro-L-norvaline. Schemes b) and c) start with ornithine derivatives protected at N5 with CBZ (benzyloxycarbonyl) and Tos (toluenesulfonate), BZL (benzyl), respectively Fig. 4b. Scheme of the synthesis of aerobactin. Protected g-hydroxynorleucine 1 (P = BOC,P = CH3) is transformed into the protected hydroxamic acid 2. Deprotection of the a-NH2 grqup enables alkylation of the o-substituted hydroxamate to give compound 3...

Aspartate and norvaline have been reported to activate several plant threonine dehydratases (Kagan et al., 1969a Bleckman et al., 1971). Low concentrations of aspartate (1-5 mM) do not, however, affect the activity of the maize enzyme under any of a number of assay conditions that have been tested (E. Lissik and J. Bryan, unpublished). Although a role of aspartate as a feedforward pathway activator would be interesting, it has not been established that this amino acid is an important effector of any plant threonine dehydratase in vivo. 

DL-Norvaline-3-C on administration to rats or on incubation with rat liver homogenates yielded radioactive a-ketovaleric acid, butyric acid, acetic acid, acetoacetate, and 3-hydroxybutyric acid HI). These compounds were isolated by column cluomatography and their identity established. Degradation of the butyric acid demonstrated that only C-2 was significantly labeled. This established that the butyrate was formed by a direct pathway from norvaline and not by the subsequent condoisation of two-carbon fragments. 

The relatively high-level isobutanol production using the amino acid pathway shows the potential of this strategy and small stepwise optimisation. This versatile approach was used for production of 1-butanol (Atsumi et al. 2008a) over the norvaline biosynthesis pathway, which is a minor side reaction of leucine biosynthesis (Connor and Liao 2009). 

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