Ehrlich pathway

The elucidation of the genetics and regulations of the Ehrlich pathway leading from amino acids to alcohols and the corresponding acids and esters—a pivotal metabolic route to flavours generated by traditional food fermentation processes—has attracted much research interest in the past. More recent inves-... 

Fig. 8D.5 Formation of higher alcohols from sugar and amino acids by the Ehrlich pathway...

Diacetyl, and its reduction products, acetoin and 2,3-butanediol, are also derived from acetaldehyde (Fig 8D.7), providing additional NADH oxidation steps. Diacetyl, which is formed by the decarboxylation of a-acetolactate, is regulated by valine and threonine availability (Dufour 1989). When assimilable nitrogen is low, valine synthesis is activated. This leads to the formation of a-acetolactate, which can be then transformed into diacetyl via spontaneous oxidative decarboxylation. Because valine uptake is suppressed by threonine, sufficient nitrogen availability represses the formation of diacetyl. Moreover, the final concentration of diacetyl is determined by its possible stepwise reduction to acetoin and 2,3-butanediol, both steps being dependent on NADH availability. Branched-chain aldehydes are formed via the Ehrlich pathway (Fig 8D.7) from precursors formed by combination of acetaldehyde with pyruvic acid and a-ketobutyrate (Fig 8D.7). 

Naturally, a major task appears to be cellular detoxification under normal and adverse growth conditions. For example, Pdrl 2 functions in the disposal of toxic weak acid catabolites that accumulate when cells are approaching the stationary growth phase [52, 55]. Pdrl2 contributes to the export of catabolic products such as phenylacetate or other carboxylic acids derived from amino acid catabolism. In this context, Pdrl 2 may be considered as an integral part of the so-called Ehrlich pathway, in which carboxylic acids are decarboxylated to the corresponding aldehyde [55,201]. 

Hazelwood, L.A., Daran, J.-M., van Maris, A.J.A., Pronk, J.T., and Dickinson, J.R. (2008) The Ehrlich pathway for fusel alcohol production a century of research on Saccharomyces cerevisiae metabolism. Appl. Environ. Microbiol, 74, 2259-2266. 

Derrick, S. and Large, P.J. (1993) Activities of the enzymes of the Ehrlich pathway and formation of branched-chain alcohols in Saccharomyces cerevisiae and Candida utilis grown... 

Already in the beginning of the nineteenth century, Felix Ehrlich identified higher alcohols, also known as fiisel oils, in alcoholic fermentations with yeast and showed that these alcohols are formed from amino acids without generating free ammonia (Ehrlich, 1907). Further studies identified the reactions of the Ehrlich pathway (i) deamination of an amino acid by a transamination reaction, (ii) decarboxylation of the 2-ketoacid to the corresponding aldehyde, and (iii) the reduction of the aldehyde to the respective alcohol (Figure 12.1 Sentheshanmuganathan and Elsden, 1958 Sentheshanmuganathan, 1960, reviewed in Hazelwood et al., 2008). 

In 2008, Atsumi et al. made use of the Ehrlich pathway by implementation of the last two reactions of this pathway into E. coli and marked the initial step toward the... 

FIGURE 12.1 The Ehrlich pathway exemplified for the conversion of the branched-chain amino acids L-valine, L-isoleucine, and L-leucine to the corresponding alcohols isobntanol, 2-methyl-1-bntanol, and 3-methyl-1-butanol. Adh, alcohol dehydrogenase KE)C, 2-ketoacid decarboxylase TA, transaminase. 

Kondo T, Tezuka H, Ishii J, Matsuda F, Ogino C, Kondo A. (2012). Genetic engineering to enhance the Ehrlich pathway and alter carbon flux for increased isobutanol production from glucose by Saccharomyces cerevisiae. J Biotechnol, 159, 32-37. 

Li S, Wen J, Jia X. (2011). Engineering Bacillus subtilis for isobutanol production by heterologous Ehrlich pathway construction and the biosynthetic 2-ketoisovalerate precursor pathway overexpression. Appl Microbiol Biotechnol, 91, 577-589. 

Higher alcohols are by-products of transamination reactions where yeasts will transfer amino groups between amino acids and a-keto-acids (Fig. 1.13). The a-keto-acids are decarboxylated into aldehydes, which are then converted into higher alcohols. Known as the Ehrlich pathway (Castor... 

Instead, all the economically viable processes developed up to now are bioconversions that employ L-phenylalanine as a substrate. Metabolic pathways have been comprehensively reviewed [63] and are briefly summarized in Scheme 9.2. The most important one, known as the Ehrlich pathway, consists of three subsequent enzymatic steps (transamination, decarboxylation, and reduction), and is considered as the basis of all bioconversion processes proposed [64]. 

Scheme 9.2 The Ehrlich pathway and other minor biochemical pathways involved in the biotechnological production of 2-phenylethanol.

Kim, B., Cho, B., and Hahn, J. (2014) Metabolic engineering of Saccha-romyces cerevisiae for the production of 2-phenylethanol via Ehrlich pathway. Biotechnol. Bioeng., Ill, 115-124. 

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