Fig. 1

The synthesis of α-functionalized organic acids by proposed modular cascade biocatalysis platform. a The engineered modular cascade biocatalysis platform. b Four general basic enzyme modules. Basic module: threonine aldolase (TA) and threonine deaminase (TD) for condensation-deamination of aldehydes and glycine to α-keto acids; extender module 1: hydroxyisocaproate dehydrogenase (HicDH) and formate dehydrogenase (FDH) for reduction of α-keto acids to α-hydroxy acid; extender module 2: ʟ-amino acid dehydrogenase (ʟ-AAD) and FDH for reduction of α-keto acids to ʟ-α-amino acids; extender module 3: D-amino acid transaminase (D-AATA), FDH, glutamate racemase (GLR), and glutamate dehydrogenase (GluDH) for transamination of α-keto acids to D-α-amino acids. Functionalized groups (α-position) and extender units (from aldehydes) are colored in red and blue, respectively. c Nine different extender units, including aromatic (1a–e), heteroaromatic (1f), heterocyclic (1g), and aliphatic (1h–i) aldehydes