Empirical rules for the enantiopreference of lipase from Aspergillus niger toward secondary alcohols and carboxylic acids, especially alpha-amino acids

Lipase from Aspergillus niger (ANL, Amano lipase AP) catalyzes enantioselective hydrolysis and acylation reactions. To aid in the design of new applications of this lipase, we propose two empirical rules that predict which enantiomer reacts faster. For secondary alcohols, a rule proposed previously for other lipases also works for ANL, but with lower reliability (77%, 37 of 48 examples). For carboxylic acids, we examined both crude and partially-purified ANL because commercial ANL contains contaminating hydrolases. Partial purification removed a contaminating amidase and increased the enantioselectivity of ANL toward many alpha-amino acids, including cyclic amino acids. Unlike other lipases, ANL readily accepts positively-charged substrates and shows the highest enantioselectivity toward alpha-amino acids. Although a rule based on the sizes of the substituents could not predict the fast-reacting enantiomer, a rule limited to alpha-amino acids did predict the fast-reacting enantiomer. We estimate that the charged alpha-amino group contributes a factor of 40-100 (Delta Delta G double dagger=2.2-2.7 kcal/mol) to the enantioselectivity of ANL towards carboxylic acids. (C) 1997 Elsevier Science Ltd.