Biosynthesis of Chemically Diversified Non-Natural Terpene Products



Executive Summary


Drug and chemical discovery is a lengthy, difficult, and inefficient process. The production of new drugs and chemicals is bottlenecked at synthesis or biosynthesis of complicated molecules, especially chiral molecules. Furthermore, diversification of current drug and chemical libraries is hindered by these difficult and inefficient synthetic processes.


Description of Technology


This technology diversifies and produces new terpene drugs and chemicals.  This technology is composed of three parts:  i) novel, non-natural enzyme substrates, ii) diterpene synthases that convert these substrates to intermediate scaffolds, and iii) the novel scaffolds.  A diverse range of new intermediates (scaffolds) was made by introducing unnatural substrate molecules to a diverse panel of substrate-agnostic class I and II diterpene synthases. These scaffolds would otherwise be impossible to synthesize using typical chemical methods or through biosynthesis with natural substrate molecules. These scaffolds can be functionalized to make new or diverse drugs, fragrances, agrochemicals, antibacterial chemicals, etc. The diterpene synthases efficiently process the new substrates into new intermediate scaffolds. The pairing of both the novel, unnatural substrate molecules and the substrate-agnostic enzymes widens the scope in drug diversification and discovery and provides a biosynthetic library for activity screening.


Key Benefits

  • Simpler and faster method: produces many diverse compounds by processing novel substrates with diterpene synthase enzymes; enzymes accept many substrates



  • All biosynthetic fields: 
    • Pharmaceuticals
    • Fragrances
    • Agrochemicals
    • Antibacterials
  • Drug and ingredient screening library
    • Forskolin analogs and derivatives
    • Neo-clerodane analogs and derivatives
    • Ingenol analogs and derivatives


Patent Status


Provisional Filed, 11/5/2019 Serial No.: 62/930,898




Prof. Edmund L. Ellsworth, Dr. Matthew Giletto, Dr. Bjoern Hamberger, Garret Miller, Dr. Richard Neubig


Tech ID




Patent Information:


For Information, Contact:

Thomas Herlache
Assistant Director
Michigan State University