Method for Producing Biliverdin IXα from a Non-Animal Source

Technical Summary

•  Dr. Jon Takemoto and Dr. Dong Chen of Utah State University’s Biology and Biological Engineering departments have developed methods to produce biliverdin IXα using Escherichia coli.

•  Using biliverdin IXα as a cytoprotective therapeutic is frequently suggested, but its clinical development and use is currently limited by insufficient quantity, uncertain purity, and derivation from mammalian materials. To address these limitations, methods to produce, recover, and purify biliverdin IXα from bacterial cultures of Escherichia coli were investigated and developed. Recombinant E. coli strains BL21(HO1) and BL21(mHO1) expressing cyanobacterial heme oxygenase gene HO1 and a sequence modified version (mHO1) optimized for E. coli expression, respectively, were constructed and shown to produce biliverdin IXα in batch and fed-batch bioreactor cultures.

 

Commercial Applications

•  Biliverdin IXα is a naturally occurring anti-inflammatory and antioxidant compound.  Biliverdin IXα may be used inter alia for the treatment of both acute and chronic inflammatory conditions and diseases, in surgical applications, as well as in organ preservation solutions.  Biliverdin IXα also acts as a cytoprotectant of pancreatic islets used in allograft transplantation procedures to reverse Type I diabetes and is known to suppress reactive oxygen species formation and oxidative stress in a number of tissues and cultured animal cells.

•  Potential commercial partners:

•  Pharmaceutical companies

•  Organ transplant groups

•  Medical and chemical supply companies

 

Competitive Advantages

•  Produced from a non-animal source

•  Highly pure

•  Scalable production by E. coli in bioreactors

•  Natural product

•  Both an antioxidant and anti-inflammatory

•  Covers broader scope of treatment than other anti-inflammatories

 

Additional Information

 

                                                                                                                     

 

              

Biliverdin IXα production by E. coli in a bioreactor

 

                                                                                                                     

 

 

Spectral and chromatographic analyses of biliverdin produced by bioreactor cultures of E. coli BL21 (mHO1)

(A) Absorbance spectra of biliverdin produced by E. coli BL21 (mHO1) (red) and commercial biliverdin IXα derived from an animal source (blue)

(B) HPLC chromatograms of biliverdin produced by E. coli BL21 (mHO1) (top) and commercial biliverdin IXα derived from an animal source (bottom)

                                                                                                                     

 

Related Technologies

•  Meso-biliverdin IXα Production and Applications (P12034)

•  Method for Production of Meso-biliverdin IXα (P11058)

 

References

•  US Patent 8,980,616

•  US Patent 8,455,222

 

Patent Information:
Category(s):
Biotech/Biomedical
For Information, Contact:
Christian Iverson
Utah State University
435-797-9620
christian.iverson@usu.edu
Inventors:
Jon Takemoto Dong Chen
Keywords:
Medicine