ABSTRACT
Aldolases, a subclass of lyases (classified as EC 4), catalyze reversible reactions. These C-C lyases (EC 4.1.x.x) typically perform a stereoselective aldol addition (or aldolization) of a donor molecule (nucleophile) on an aldehyde acceptor molecule (electrophile) (Brovetto et al., 2011; Clapés et al., 2010a; Clapés and Garrabou, 2011; Fesko and Gruber-Khadjawi, 2013; Machajewski and Wong, 2000; Samland and Sprenger, 2006). On the other side, they can split a larger molecule into these smaller moieties (retro-aldol reaction or cleavage). In biochemistry, aldolases play important roles in the formation or cleavage of carbohydrates, sugar acids, and amino acids (Samland and Sprenger, 2006). As a well-known example from glycolysis, D-fructose-1,6-bisphosphate aldolase (FBP aldolase or FruA, EC 4.1.2.13) reversibly cleaves D-fructose-1,6-bisphosphate into the triose compounds, dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (Ga3P). During gluconeogenesis, the same enzyme forms the bisphosphate. Other aldolases are involved in the degradation of sugar acids or aromatic C-sources (Clapés et al., 2010a; Samland and Sprenger, 2006), or are involved in biosynthetic reactions. Most aldolases catalyze the addition of a ketone onto an aldehyde acceptor (Table 21.1, entries 1-3), but some others use either an amino acid (glycine, alanine; Table 21.1, entry 5), or an aldehyde (acetaldehyde, glycolaldehyde;
Table 21.1, entries 2 and 4) as donor (Brovetto et al., 2011; Clapés et al., 2010a). Stereoselectivity is generally governed by the specific aldolase enzyme. Table 21.1 Classification of aldolases by donor specificity
Note: Column 1 gives the most commonly used donor compounds for aldolases, column 2 possible products in a generic presentation, and column 3 examples of industrially relevant products.Aldolases can be classified either by their reaction mechanism (class I and class II aldolases, pyridoxal-phosphate enzymes), or by their donor substrate specificity (Clapés et al., 2010a; Clapés and Garrabou, 2011; Dean et al., 2007; Fesko and Gruber-Khadjawi, 2013): Class I aldolases do not need a cofactor. Instead, they activate the donor compound by formation of a covalent intermediate, which is a protonated Schiff base formed between a lysyl residue and the carbonyl carbon of the donor substrate (Clapés et al., 2010a; Machajewski and Wong, 2000; Samland and Sprenger, 2006). This activated donor then adds stereoselectively to the acceptor aldehyde.
