Reconstructing enzymes for novel nitrogen-nitrogen bond forming chemistry

Introduction

Nitrogen-nitrogen (N-N) bonds have fascinating structural and functional properties. They are ubiquitously found in diverse pharmaceuticals and fine chemicals and represent important key structural motifs in various natural products, endowing them with potent biological activities.

Challenges in Synthesis

However, traditional chemical procedures to synthesize N-N bond-containing compounds are often difficult to realize, costly, and environmentally unfriendly. In addition, the formation of intermolecular N-N linkages is particularly difficult and remains a mostly unaddressed problem in chemistry.

Project Overview

ReCNNSTRCT will address this challenge by decoding novel reaction chemistries from the underexploited family of N-N bond-forming enzymes (NNZYMES). The project will tackle reactions that are difficult to realize by traditional chemical approaches and currently not feasible by enzyme catalysis.

Objectives

As such, ReCNNSTRCT aims to break new ground in chemical synthesis by:

1. Developing an enzymatic toolbox for versatile N-N bond-forming reaction chemistries.
2. Exploring naturally promiscuous and redesigned NNZYMES for diverse intra- and intermolecular, as well as non-natural N-N bond formations.

Methodology

To achieve this, ReCNNSTRCT will combine methodologies from:

• Enzyme catalysis and evolution
• Genome mining
• The latest achievements in bioinformatics

In this way, ReCNNSTRCT will not only establish the chemistry performed by the enzymes but will also elucidate enzyme structures, catalytic mechanisms, and design biocatalytic cascades to showcase the potential of tailored NNZYMES.

Impact

ReCNNSTRCT will thus revolutionize our synthetic strategies and aims to substantially contribute to a greener chemical industry by creating versatile catalytic platforms for N-N bond formation. This will lead to streamlined routes to high-value chemicals.

Beyond this groundbreaking direct impact in the field of enzyme catalysis, ReCNNSTRCT will boost the clinical and research environment by providing new biocatalysts for future drug discovery efforts.