Fig. 1: Amide bond-forming enzyme(s) are hypothesized to be involved in the biosynthesis of E-64.
From: Enzymatic combinatorial synthesis of E-64 and related cysteine protease inhibitors
a, Structure, mode of action and retrobiosynthesis of 1. E-64 contains the t-ES warhead that is the site of covalent inhibition of cysteine proteases. E-64 is proposed to form from the condensation of (2S,3S)-t-ES, l-Leu and agmatine. b, Structures of synthetic cysteine protease inhibitors based on 1. c, Structure of dapdiamide E. d, Mechanism and application of bacterial ABSs such as McbA from the marinacarboline biosynthetic pathway. e, Mechanism and applications of bacterial ATP-grasp enzymes such as TabS from the tabtoxin biosynthetic pathway. f, Stepwise combination of two bacterial amide bond-forming enzymes CysC and CysD to synthesize cystargolide analogs. g, In this work, we discovered and biochemically characterized the fungal ATP-grasp enzyme and ABS from the biosynthesis of 1 and used the enzymes in the synthesis of diverse E-64 analogs.
