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Enzymatic production of new therapeutic β-lactones

Technology #20170348

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Schematic showing the discovered enzymatic pathway of β-lactone production that is used to create new β-lactone compounds.
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Researchers
Lawrence P. Wackett, PhD
Professor, Biochemistry, Molecular Biology, and Biophysics
External Link (cbs.umn.edu)
Managed By
Kenneth Karanja
Technology Licensing Officer 612-624-4531
Patent Protection

US Patent Pending
Publications
β-Lactone synthetase found in olefin biosynthesis pathway
Biochemistry, 56, 2: 348-351, 2017
Active multi-enzyme assemblies for long-chain olefinic hydrocarbon biosynthesis
Journal of Bacteriology, 199,9, e00890-16, May 2017

Biological production of diverse β-lactones

This technology is a method for creating a wide variety of β-lactones using enzymatic production. β-lactones have shown strong therapeutic properties including antimicrobial activity. This emerging class of compounds also includes the only FDA approved anti-obesity drug (orlistat) and a potent anti-cancer drug (marizomib) in phase III clinical trials for glioblastoma. However, having been historically difficult to synthesize and purify, only a handful of new β-lactones have been isolated annually. Using bacterial enzymes responsible for β-lactone synthesis, this technology makes it possible for the first time to synthesize hundreds of different β-lactones for therapeutic development.

Nature’s specialized and expansive toolkit delivers a myriad of new compounds

The current methods for producing β-lactones include purification from microbes and chemical synthesis, both of which are incredibly challenging because of the natural reactivity of β-lactones. This technology bypasses these challenges by purifying and employing the enzymes (OleA, OleC and OleD) used by a variety of bacteria to synthesize β-lactones from more readily available substrates (3-hydroxy acid, acyl-CoA, carboxylic acids, or fatty acids). Furthermore, the development of an algorithm to identify β-lactone producing genes in hundreds of bacterial strains has provided more enzymes to make an ever-expanding set of these molecules. This technology provides the ability to form the first-ever β-lactone library, making it possible to evaluate the full therapeutic potential of these compounds.

Phase of Development

  • Novel compounds synthesized. Demonstrated ability to make novel β-lactone compounds that can be used to form a library and/or assessment in therapeutic applications.

Benefits

  • Fewer resources spent on compound synthesis: Enzymatic production of β-lactones exponentially increases the number of compounds that can be created, saving time, energy and cost typically spent on compound synthesis.
  • High return probability: The ability to create a library of β-lactone compounds that can be screened for therapeutic activity creates a high probability of identifying positive hits.
  • Design with molecular precision: Allows the controlled production of enantiopure trans- and cis-lactones.

Features

  • Bypasses synthesis and purification challenges
  • Large number of β-lactones that can be produced
  • Production of truly novel compounds

Applications

  • β-lactone library creation
  • Therapeutic compound discovery and development
  • β-lactone synthesis kits


Interested in Licensing?
The University relies on industry partners to further develop and ultimately commercialize this technology. The license is for the sale, manufacture or use of products claimed by the patents. Please contact Kenneth Karanja to share your business needs and licensing and technical interests in this technology.