Discovery of novel deaminases and developing better enzyme-based technologies for genomics and epigenomics applications

We work closely with experimental scientists in the Research and Application Development Departments to discover novel enzymes and develop new enzyme-based high-throughput methodologies and analytical tools, propelling forward the frontiers of genomics and epigenomics.

Recently, we have screened over 200 new cytosine deaminase variants from various protein and metagenomics databases by integrating bioinformatics, in-vitro protein synthesis, LC/MS-based analytical chemistry, and high-throughput sequencing approaches. Our work has identified many new cytosine deaminases with interesting and previously undiscovered properties. Among these were enzymes with strong activity on double and single-stranded DNA without any apparent sequence constraints, enzymes that do not deaminate modified cytosines, and enzymes with a variety of sequence context preferences, including a preference for CpG. These novel properties are highly desired for converting deaminases into powerful and easy-to-use tools for detecting epigenetic modifications and for genome editing. For example, we recently demonstrated the utility of a non-specific double-strand modification-sensitive deaminase in a streamlined EM-seq protocol that eliminated the denature step as well as the usage of all the other cytosine modifying enzymes. This new deaminase is transforming the EM-seq method into a single-enzyme-one-tube protocol and potentially enables single-cell applications. We believe this new protocol will not only facilitate new advancements in epigenetics for research and clinics but will also give NEB an advantage in the epigenetics product market.

We are also collaborating with Erbay Yigit’s group to look for new deaminases with RNA activities and other enzymes that can modify RNA in different ways.