Mapping enzyme catalysis with metabolic biosensing

Abstract

Enzymes are represented across a vast space of protein sequences and structural forms and have activities that far exceed the best chemical catalysts; however, engineering them to have novel or enhanced activity is limited by technologies for sensing product formation. Here, we describe a general and scalable approach for characterizing enzyme activity that uses the metabolism of the host cell as a biosensor by which to infer product formation. Since different products consume different molecules in their synthesis, they perturb host metabolism in unique ways that can be measured by mass spectrometry. This provides a general way by which to sense product formation, to discover unexpected products and map the effects of mutagenesis.

Document Details

Document Type
Pub Defense Publication
Publication Date
Nov 23, 2021
Source ID
10.1038/s41467-021-27185-9

Entities

People

  • Adam R. Abate
  • Claire M Palmer
  • Cyrus Modavi
  • Dale S. Cornett
  • Emory M Payne
  • Hal S. Alper
  • Kai-chun Chang
  • Leqian Liu
  • Linfeng Xu
  • Nannan Tao
  • Robert T. Kennedy

Organizations

  • Division of Chemistry
  • National Institutes of Health
  • Office of the Director of National Intelligence
  • United States Department of Health and Human Services

Tags

Fields of Study

  • Chemistry

Readers

  • Molecular Genetics
  • Organic Chemistry
  • Theoretical Analysis.

Technology Areas

  • AI & ML
  • Biotechnology
  • Space