In conclusion, we developed a new-to-nature biocatalytic asymmetric alkylation of benzaldehydes and a-keto acids via a radical mechanism. Through the cooperative interactions between a judiciously selected photoredox catalyst and a set of engineered TPP enzymes, we advanced a novel thiamine radical biocatalysis platform to realize free radical reactions that are not encountered in biology with excellent enantiocontrol. In particular, two distinct TPP enzyme variants derived from the BFD and BAL families were engineered via high-throughput experimentation under photochemical conditions, displaying complementary reactivity profiles in this radical transformation. We expect that a wide range of synthetically useful asymmetric radical reactions will be developed through new-to-nature thiamine radical biocatalysis. • ee of 4a (PpBFD H281V) ee of 4a (PfBAL T481L A480L)