Ancestral Sequence Reconstruction to Enable Biocatalytic Synthesis of Azaphilones.

ABSTRACT: Biocatalysis can be powerful in organic synthesis but is often limited by enzymes' substrate scope and selectivity. Developing a biocatalytic step involves identifying an initial enzyme for the target reaction followed by optimization through rational design, directed evolution, or both. These steps are time consuming, resource-intensive, and require expertise beyond typical organic chemistry. Thus, an effective strategy for streamlining the process from enzyme identification to implementation is essential to expanding biocatalysis. Here, we present a strategy combining bioinformatics-guided enzyme mining and ancestral sequence reconstruction (ASR) to resurrect enzymes for biocatalytic synthesis. Specifically, we achieve an enantioselective synthesis of azaphilone natural products using tw

SUBMITTER: Chiang CH 

PROVIDER: S-EPMC11923553 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature