Disorazole Z Fermentation Stability

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Solution Overview

Problem

Current secondary metabolites from myxobacteria of the genus Sorangium lack novel compounds with effective antifungal, antibiotic, and cytotoxic properties, and have stability issues in medical formulations.

Innovation Solution

Development of novel compounds Disorazole Z and Disorazole Z-epoxide with unique cyclic core structures, produced through fermentation of Sorangium myxobacteria, offering improved stability and biological activity for medical use.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If known Disorazoles and Chivosazoles are used as secondary metabolites from Sorangium myxobacteria, then biological activities (antibiotic, antifungal, cytotoxic) are achieved, but structural novelty and long-term stability in formulations are insufficient

Engineering Contradiction:
Improvelong-term stabilityVSAvoidstructural novelty
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent segments the macrolide ring structure into distinct functional regions with specific stereochemical configurations, creating novel compounds with improved stability. The asymmetric carbon atoms at positions 3 and 3' are specifically configured to enhance formulation stability while maintaining biological activity.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent changes key structural parameters including the configuration of asymmetric carbon atoms (R/S configurations at positions 3 and 3'), the arrangement of double bonds (Z/E isomers), and the specific substituent patterns. These parameter changes result in compounds with enhanced long-term stability compared to known Disorazoles and Chivosazoles.

Inventive Principle:
Principle #35Parameter changes

2Manufacturing precision

If standard chemical synthesis procedures are used to produce novel compounds, then structural precision is achieved, but production complexity and time increase

Engineering Contradiction:
Improvestructural precisionVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent utilizes the natural biosynthetic capabilities of Sorangium myxobacteria to self-produce the novel Disorazole Z compounds. The microorganism's metabolic pathways automatically perform the complex stereochemical transformations that would require multiple synthetic steps, significantly improving production efficiency while maintaining structural precision.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces complex chemical synthesis mechanisms with biological fermentation mechanisms. The enzymatic systems within Sorangium myxobacteria naturally perform the stereoselective transformations, substituting the need for complex mechanical synthesis apparatus and multiple purification steps with a self-organizing biological system.

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

3Productivity

If fermentation of Sorangium myxobacteria is used to produce compounds, then productivity is improved, but process complexity and purification difficulty increase

Engineering Contradiction:
Improveproduction outputVSAvoidfermentation process complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent employs preliminary action by pre-culturing Sorangium myxobacteria under specific conditions that maximize compound production before the main fermentation process. The inoculum is prepared with optimized nutrient composition and physiological state, ensuring high productivity from the start of production while simplifying downstream processing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent applies discarding and recovering principles in the fermentation process by allowing the microorganism to consume excess nutrients and metabolic byproducts during growth phases, then recovering the accumulated Disorazole Z compounds in high purity during the stationary phase, simplifying the overall purification process.

Inventive Principle:
Principle #34Discarding and recovering

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

The compounds demonstrate potent antifungal, antibiotic, and cytotoxic activities, with enhanced stability in pharmaceutical preparations, suitable for treating chronic inflammatory diseases and tumors, and can be synthesized through standard chemical procedures or fermentation.

Implementation Method 1

The compounds are currently named Disorazole Z and Disorazole Z-epoxide, respectively, with a specific configuration of unsaturated bonds with its cyclic core structure... produced through fermentation of Sorangium myxobacteria

Methodology Applied
Scientific EffectFermentation: Fermentation

Data Source

PatentEP1904505B1Biologically active compounds obtainable from sorangium cellulosum
Publication Date: 2013.07.17 HELMHOLTZ ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH
  • EP1904505B1 patent drawingFigure 1
  • EP1904505B1 patent drawingFigure 2A~2E
  • EP1904505B1 patent drawingFigure 2F~2K

AI summary

The present invention relates to a novel group of compounds having antibiotic, antifungal and/or cytostatic properties, which are obtainable from myxobacteria, especially of the genus Sorangium, preferably Sorangium cellulosum. One representative of this group of compoundsis currently named Disorazole Z and Disorazole Z-epoxide, respectively, with specific substituents and specific unsaturated bonds to its cyclic core structure (I) and (II).