a key transformation in organic synthesis because it builds the backbone of most organic molecules . Chemists have developed a variety of methods for catalysing this type of transformation but it still poses a challenge , often requiring complex catalysts and strict reaction conditions to control stereoselectivity . Biocatalysis is becoming increasingly popular for linking two carbon atoms economically and efficiently by nature ’ s own catalysts , enzymes . However , natural enzymes are often not industrially applicable , due to low activity with non-natural substrates and poor stability under technical process conditions . Enzyme engineering by directed evolution facilitates overcoming this obstacle by reducing substrate and / or product inhibition and increasing solvent tolerance , thermostability , and stereo- , regio- and chemo-selectivity . ¹

Amino acids via decarboxylase

The production of amino acids using enzymes is well established and reviewed . 2 Lyases , amino acid dehydrogenases and aminotransferases are typical enzyme classes deployed for amino acid synthesis .

A commonly used application is the production of L-alanine by decarboxylases . One industrial process is the decarboxylation of L-aspartic acid with a L-aspartate β-decarboxylase using a continuously operated reaction that was set up by Tanabe Seiyaku ( now Mitsubishi Pharma ). ³ Enzymaster applies another decarboxylase , L-aspartate-αdecarboxylase , to produce β-alanine industrially , also starting from L-aspartic acid as the substrate ( Figure 1a ). However , the wildtype L-aspartate-α-decarboxylase showed rather low activity and poor

Figure 1 – Decarboxylasecatalysed conversion of L-aspartic acid to ß-alanine ( a ), enzymatic synthesis ( b ) of L-tyrosine using tyrosine phenollyase & enzymatic synthesis of ( 2S , 3R ) -2- amino-3-hydroxy- 3- ( 4-nitrophenyl ) propanoic acid by engineered aldolase starting from p-nitrobenzaldehyde & glycine ( c )

40 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981