3-Hydroxyindolenines can be used to access several structural motifs that are featured in natural products and pharmaceutical compounds, yet the chemical synthesis of 3-hydroxyindolenines is complicated by overoxidation, rearrangements, and complex product mixtures. The selectivity possible in enzymatic reactions can overcome these challenges and deliver enantioenriched products. Herein, we present the development of an asymmetric biocatalytic oxidation of 2-arylindole substrates aided by a curated library of flavin-dependent monooxygenases (FDMOs) sampled from an ancestral sequence space, a sequence similarity network, and a deep-learning-based latent space model. From this library of FDMOs, a previously uncharacterized enzyme, Champase, from the Valley fever fungus, Coccidioides immitis strain RS, was found to stereoselectively catalyze the oxidation of a variety of substituted indole substrates. The promiscuity of this enzyme is showcased by the oxidation of a wide variety of substituted 2-arylindoles to afford the respective 3-hydroxyindolenine products in moderate to excellent yields and up to 95:5 er.