Farnesylated Dibenzodiazepinone Fermentation Yield via pH Adjustment
Solution Overview
Problem
Current fermentation methods for producing the farnesylated dibenzodiazepinone ECO-4601 are limited in scale and yield, requiring increased equipment and solvent volumes, and lack efficiency in extracting and stabilizing the compound for pharmaceutical use.
Innovation Solution
A scalable process involving fermenting a microorganism capable of producing ECO-4601, adjusting the fermentation broth to associate the compound with particulate matter, harvesting and extracting it with a suitable organic solvent, and treating the extract to achieve a high concentration of ECO-4601, which is then crystallized for pharmaceutical formulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If fermentation scale is increased to produce more ECO-4601, then productivity increases, but equipment volume and solvent volumes must be increased
Solution Approach 1:
The patent changes the concentration parameter of ECO-4601 in the fermentation broth from typical low concentrations to greater than 50-fold concentration through a multi-step process involving pH adjustment to associate the compound with particulate matter, harvesting the particulate matter, and extracting with organic solvent. This parameter change allows high productivity without proportionally increasing equipment volume.
Solution Approach 2:
The patent segments the production process into distinct stages: fermentation, pH adjustment, particulate matter harvesting, extraction, and concentration. This segmentation allows each stage to be optimized independently, achieving high final concentration without requiring large-scale equipment at each step.
2Quantity of substance
If conventional extraction methods are used, then the compound can be isolated, but the concentration achieved is insufficient for pharmaceutical formulation
Solution Approach 1:
The patent applies preliminary action by adjusting the pH of the fermentation broth before extraction to associate ECO-4601 with particulate matter. This preliminary step concentrates the compound in a harvestable form, making subsequent extraction more efficient and achieving the required concentration for pharmaceutical formulation.
Solution Approach 2:
The patent uses particulate matter as an intermediary to facilitate concentration of ECO-4601. The compound associates with the particulate matter during pH adjustment, allowing it to be harvested and then extracted with organic solvent to achieve high concentration in the final extract.
3Ease of operation
If fermentation broth is directly processed without pH adjustment, then the process is simpler, but ECO-4601 does not associate with particulate matter for efficient harvesting
Solution Approach 1:
The patent changes the pH parameter of the fermentation broth to a specific range that promotes association of ECO-4601 with particulate matter. This parameter change is a simple operational step that reliably ensures the compound associates with particulate matter for efficient harvesting and concentration.
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 process achieves a significant increase in ECO-4601 yield, stability, and scalability, allowing for efficient extraction and formulation into pharmaceutical compositions without the need for additional equipment or solvent volumes, enabling commercial production and clinical trials.
Implementation Method 1
a) fermenting a strain of a microorganism capable of producing said farnesylated dibenzodiazepinone in an aqueous culture medium thereby producing a fermentation broth comprising said farnesylated dibenzodiazepinone
Implementation Method 2
b) adjusting said fermentation broth to allow said farnesylated dibenzodiazepinone to associate with a particulate matter present in said broth
Implementation Method 3
d) extracting said harvested particulate matter with a volume of a suitable organic solvent in a proportion of about 2:1 to about 5:1 to said harvested particulate matter to thereby form an extract
Implementation Method 4
e) treating said extract to form a first concentrate comprising said farnesylated dibenzodiazepinone, wherein said first concentrate comprises said farnesylated dibenzodiazepinone at a concentration greater than about 50-fold than said farnesylated dibenzodiazepinone in said fermentation broth
Implementation Method 5
The process achieves a significant increase in ECO-4601 yield, stability, and scalability, allowing for efficient extraction and formulation into pharmaceutical compositions
Data Source
AI summary
The present invention provides a scalable process for producing a concentrate containing a mass of a farnesylated dibenzodiazepinone by fermenting in an aqueous culture medium a strain of a microorganism that is capable of producing the farnesylated dibenzodiazepinone, upon completion of fermentation harvesting the fermentation broth and extracting the fermentation broth to provide an extract, and thereafter treating the extract to form the concentrate. The concentrate so produced may be utilized in downstream processes for producing pharmaceutical compounds. A strain of a Micromonospora species capable of producing a farnesylated dibenzodiazepinone at a high yield rate is provided, together with culture media for culturing microorganisms, and fermentation conditions for production of the farnesylated dibenzodiazepinone of the concentrate.