Cyclic Peptide Production Enzymes and System



Executive Summary


Cyclic peptides tend to be resistant to peptidases and therefore stable in vivo. Their size, chemical properties, and ability to interact with biomolecules suggest that they make good pharmaceutical and agricultural active ingredient candidates.  However, intra-molecular cyclization is difficult and competes with unwanted inter-molecular polymerization reactions. Our technology is a stable, scalable, and cost-effective cyclic peptide production platform to feed growing demands in pharmaceutical and agricultural active ingredient discovery projects. The platform allows for engineering and production of a wide range of cyclic peptides. 


Description of Technology


This technology is an enzymatic system for making cyclic and bi-cyclic peptides. The POPB enzyme from various fungi is able to cyclize a wide variety of pre-peptides. POPB is able to make cyclic peptides from 8 to 16 amino acids from a pre-peptide. With additional structural constraints, 7-mer cyclic peptides may also be made. POPB will cyclize pre-peptides containing non-standard amino acids, including D-amino acids and hydroxylated amino acids, greatly expanding the potential size of cyclic peptide chemical libraries synthesized by POPB. Observed in vitro cyclization efficiencies approach 100%, without inter-molecular polymerization. An additional enzyme, FMO1, may be used to introduce an unusual tryptothionine cross bridge into the cyclic peptide, further stabilizing the peptide and increasing conformational stability of the peptide ring. This cyclic peptide production platform provides a stable, scalable, and cost-effective method of making of these biologically active compounds for pharmaceutical and agricultural active ingredient discovery. 


Key Benefits

  • Enable cost-effective, scalable biosynthetic production of rare, complex cyclic peptides and natural products
  • Provide reliable supply for clinical research
  • Produce a very large library of novel chemical composition
  • Cyclic peptides are promising compounds for drug discovery in high throughput screens:
    • Small molecules with excellent stability & promising bioavailability characteristics
    • Cyclic structure prevents cyclic peptides from being attacked by proteinases



  • Cyclic peptide production
  • Therapeutics/drug discovery
  • Agricultural Active Ingredients


Patent Status:


US Patents 9,273,100 and 9,598,686 and two patents pending (15/437,359 and 62/491,632)


Licensing Rights Available


Full licensing rights available.


Inventors: Dr. Jonathan Walton, Dr. Heather Hallen, Dr. John Scott-Craig


Tech ID: TEC2012-0019


Patent Information:

For Information, Contact:

Thomas Herlache
Assistant Director
Michigan State University