Meso-biliverdin IXα Production via Microbial Conversion

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Solution Overview

Problem

Current therapeutic options for inflammation and transplantation processes lack effective alternatives to biliverdin IXα, which is being investigated for its potential benefits, necessitating the development of new compounds and methods for treating various clinical applications.

Innovation Solution

The development of meso-biliverdin IXα (MBV) compositions and methods for production, including microbial production, phycocyanobilin extraction, and conversion, as well as its use in pharmaceutical compositions for treating inflammation and transplantation processes, offering a new therapeutic approach.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If biliverdin IXα is used as a therapeutic for inflammation and transplantation, then anti-inflammatory effects are achieved, but additional and alternative therapeutics are needed to expand treatment options

Engineering Contradiction:
Improvetherapeutic optionsVSAvoidavailable compounds
Core Design Contradiction:
Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent segments the biliverdin molecule by creating isomers with different stereochemical configurations at specific carbon positions (C-2, C-3, C-4, C-5, C-6, C-7, C-8, C-9, C-10, C-11, C-12, C-13, C-14, C-15, C-16, C-17, C-18, C-19, C-20, C-21, C-22, C-23, C-24, C-25, C-26, C-27, C-28, C-29, C-30, C-31, C-32, C-33, C-34, C-35, C-36, C-37, C-38, C-39, C-40, C-41, C-42, C-43, C-44, C-45, C-46, C-47, C-48, C-49, C-50, C-51, C-52, C-53, C-54, C-55, C-56, C-57, C-58, C-59, C-60, C-61, C-62, C-63, C-64, C-65, C-66, C-67, C-68, C-69, C-70, C-71, C-72, C-73, C-74, C-75, C-76, C-77, C-78, C-79, C-80, C-81, C-82, C-83, C-84, C-85, C-86, C-87, C-88, C-89, C-90, C-91, C-92, C-93, C-94, C-95, C-96, C-97, C-98, C-99, C-100). This segmentation approach generates multiple distinct compounds (isomers) from a single parent molecule structure, thereby expanding the quantity of available therapeutic compounds while maintaining the core anti-inflammatory mechanism of action

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent applies parameter changes by modifying the stereochemical configuration parameters of the biliverdin molecule at specific chiral centers. By systematically varying the R/S configuration at different carbon positions, the invention generates a library of isomeric compounds with potentially differentiated pharmacological properties, thus expanding therapeutic options while based on a proven molecular scaffold

Inventive Principle:
Principle #35Parameter changes

2Productivity

If existing production methods for biliverdin IXα are used, then therapeutic compound is obtained, but production safety and efficiency can be improved

Engineering Contradiction:
Improveproduction efficiencyVSAvoidproduction safety
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent employs microbial systems (bacteria, yeast, or fungal cells) that possess endogenous heme oxygenase enzyme activity to autonomously convert heme to biliverdin and subsequent isomers. The microbial cells self-service by utilizing their own metabolic pathways and enzyme systems to produce the therapeutic compounds, eliminating the need for complex chemical synthesis procedures and improving both safety and efficiency

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces mechanical/chemical synthesis methods with biological conversion processes. Instead of using chemical reagents and complex multi-step synthesis protocols, the invention utilizes living microbial systems to catalyze the conversion of heme to biliverdin isomers through enzymatic reactions, thereby simplifying the production process and improving safety by eliminating hazardous chemicals

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

MBV demonstrates effectiveness in reducing inflammation and enhancing organ viability for transplantation by interacting with biliverdin reductase enzymes, promoting anti-inflammatory processes and improving islet cell yields, while providing a safer and more efficient production method compared to existing processes.

Implementation Method 1

MBV demonstrates effectiveness in reducing inflammation and enhancing organ viability for transplantation by interacting with biliverdin reductase enzymes

Methodology Applied
Scientific EffectEnzyme interaction: Enzyme

Implementation Method 2

In biological processes, BV IXα is known to undergo conversion to bilirubin IXα that in turn associates with cell membranes where it quenches the propagation of reactive oxygen species

Methodology Applied
Scientific EffectBiological conversion:

Data Source

PatentUS9119842B2Therapeutic meso-biliverdin IXα compositions and associated methods
Publication Date: 2015.09.01 UTAH STATE UNIVERSITY
  • US9119842B2 patent drawing
  • US9119842B2 patent drawing
  • US9119842B2 patent drawing

AI summary

Methods and materials for treating various diseases and medical conditions with meso-biliverdin compositions. In addition methods and materials for producing meso-biliverdin are provided where the methods include reacting phycocyanobilin with an amphoteric compound in a solvent to yield meso-biliverdin are provided.