Directed evolution is a powerful technique for the creation of novel biocatalysts that have many applications in organic synthesis and biotechnology. It promises to eliminate limited substrate scope, insufficient activity, and poor regioselectivity or stereoselectivity of natural biocatalysts. This approach has not been utilized to its full potential because of shortcomings in common PCR-based mutagenesis techniques, such as error prone PCR (epPCR) and saturation mutagenesis (SM). Here we show how these issues can be mitigated by using high fidelity solid-phase chemical gene synthesis on silicon chips, followed by efficient gene assembly, for combinatorial library construction.