Biosynthetic Gene Cluster for the Peptide Antibiotic Enduracidin

Summary

 

Technology Description

 

To produce a library of S. fungicidicus mutants, an in vitro transposon-based method was devised to randomly insert a selectable marker and oriT element in fosmid inserts carrying segments of the enramycin biosynthetic gene cluster and adjacent regions. This library of mutagenized fosmids was screened to identify specific disrupted genes. The collection of mutagenized fosmids was then introduced to the parent wild-type Streptomyces sp. to create a cluster-wide disruption library. Advantageous mutations were identified leading to organisms that biosynthesize different enduracidin analogs. Exemplary enduracidin analogs synthesized by this method include tetrahydrorenduracidin A, tetrahydroenduracidin B, deschloroenduracidin A, and deschloroenduracidin B.

 

Features & Benefits

 

  • Provides the potential to produce millions of random disruptions for a large library of analogs
  • Analogs for improved therapeutic properties

 

Applications

 

  • Drug discovery
  • Feed Additives

 

Background of Invention

 

The emerging and persistent threat of multidrug-resistant bacterial infections has resulted in enormous healthcare costs and poses major challenges to public health. To address the need for new antibiotics capable of combating the gowning problem of resistance, Oregon State University researchers cloned and patented the biosynthetic gene cluster for Enramycin, which is a peptide antibiotic produced in S. fungicidicus and widely used as a feed additive for pigs and chickens, and also developed methods for generating a library of enramycin analogs.

 

 

Status

 

U.S. patent no. 8,188,245 ; available for exclusive or non-exclusive licensing in a field limited to human health and therapeutics.

 

Patent Information:
Tech ID:
OSU-06-38
Category(s):
Therapeutics
Contact:
Joe Christison
IP & Licensing Manager
Oregon State University
541-737-9016
joe.christison@oregonstate.edu
Inventors:
T. Mark Zabriskie
Xihou Yin
Keywords:
Biomedical
Biotechnology
Medical Science & Technologies
Pharmaceuticals
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