Xenoprotein engineering via synthetic libraries

Abstract

Combinatorial protein libraries—prepared via molecular biology-based approaches—are invaluable tools for protein engineering. The inclusion of noncanonical amino acids in such libraries is of considerable interest. However, at present no approach competes with chemical synthesis in terms of the variety and number of noncanonical amino acids that can be simultaneously incorporated into a protein molecule. Here, we describe selection from synthetic libraries as a strategy for protein engineering. The approach enables identification of small (∼30 aa), functional protein variants comprising a virtually unlimited variety of noncanonical amino acids. Increasing the throughput of synthetic library screening, which was achieved through this effort, is anticipated to improve the utility of synthetic libraries for identifying polypeptide-based ligands with de novo function.

Document Details

Document Type
Pub Defense Publication
Publication Date
May 21, 2018
Source ID
10.1073/pnas.1722633115

Entities

People

  • Alexander A Vinogradov
  • Alexander J. Mijalis
  • Anthony J. Quartararo
  • Anupam Bandyopadhyay
  • Bradley L. Pentelute
  • Eric A. Standley
  • Ethan D Evans
  • Evan D. Styduhar
  • Faycal Touti
  • Jessica L. Wilson
  • Jessica M. Weber
  • Kathryn H. Halloran
  • Mark D. Simon
  • Sarah Z. Tasker
  • Surin K. Mong
  • Timothy F. Jamison
  • Zachary P. Gates
  • Zi-ning Choo

Organizations

  • Massachusetts Institute of Technology

Tags

Readers

  • Distributed Systems and Data Platform Development
  • Molecular and Cellular Biochemistry
  • Nanocomposite Materials Science

Technology Areas

  • Biotechnology