An engineered (S)-selective imine reductase from Streptomyces sp. GF3546 (SIR46) showed twice the activity of the wild type and high thermostability at 50 °C. Using a biocatalyst based on SIR46, we investigated the activity toward high-concentration 2-methyl-1-pyrroline up to 500 mM, conversion rates of other imines, and reductive amination activity.