Colchicinoid Biotransformation via Enzyme Induction
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Solution Overview
Problem
Existing biotransformation processes for producing 3-O-glycosyl derivatives of colchicinoid compounds are limited by low productivity and longer processing times, with significant accumulation of intermediates leading to inhibition and reduced conversion yields.
Innovation Solution
A multiple feed-batch fermentation process using demethylated colchicinoids to induce the glycosylating enzyme system, allowing for early activation and efficient conversion of colchicinoids, with fractionated feeding of substrates and carbon sources to enhance productivity and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional biotransformation processes are used with initial substrate concentration up to 1 g/l, then conversion yield reaches up to 90%, but total productivity and specific productivity remain limited
Solution Approach 1:
The patent applies preliminary action by adding demethylated colchicinoids (inducers) at the beginning of the biotransformation process to activate the glycosylating enzyme system before the main substrate is added. This pre-activation allows the system to handle higher substrate loads more efficiently, thereby increasing total productivity without sacrificing conversion yield.
Solution Approach 2:
The patent changes the parameter of initial substrate concentration from the conventional 1 g/l to significantly higher levels (2-4 g/l) by modifying the enzyme system's readiness through inducer addition. This parameter change enables higher total substrate transformation while maintaining high conversion yields through the pre-activated glycosylating system.
2Productivity
If conventional biotransformation processes are used, then conversion yield reaches up to 90%, but processing time extends to 26-28 hours
Solution Approach 1:
By adding demethylated colchicinoids as inducers at the start of the process, the glycosylating enzyme system is activated in advance. This preliminary activation reduces the lag phase and accelerates the biotransformation rate, thereby decreasing processing time from 26-28 hours to a shorter duration while maintaining high specific productivity.
Solution Approach 2:
The patent ensures continuity of useful action by maintaining high enzyme activity throughout the process through proper inducer addition. This continuous efficient conversion eliminates idle time and maintains high reaction rates throughout, reducing overall processing time while preserving high productivity.
3Productivity
If higher substrate amounts are transformed, then total productivity increases, but intermediate accumulation occurs leading to inhibition and reduced conversion yields
Solution Approach 1:
The patent applies preliminary action by pre-activating the glycosylating enzyme system with demethylated colchicinoid inducers before adding high amounts of substrate. This ensures the system is ready to immediately and efficiently convert substrate as it becomes available, preventing intermediate accumulation even at high substrate loads, thus maintaining both high productivity and reliable conversion yields.
Solution Approach 2:
The patent implements a form of feedback control where the inducer addition creates a self-regulating system. The demethylated colchicinoids induce the glycosylating enzyme system in proportion to the substrate load, allowing the system to automatically adjust its capacity to handle higher substrate amounts without intermediate accumulation, thereby maintaining conversion yield reliability.
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
This approach significantly increases total and specific productivity, reduces processing time, and maintains high conversion yields, resulting in a faster and more efficient production of high-purity 3-O-glycosylcolchicinoid compounds with improved downstream processing and environmental compatibility.
Implementation Method 1
the enzyme involved in the glycosylation step is efficiently induced by demethylated colchicinoids such as 3-O-demethylcolchicine (DMC) or 3-O-demethylthiocolchicine (DMTC)
Implementation Method 2
The process of the invention consists of a multiple feed-batch fermentation process
Data Source
AI summary
The present invention relates to a biotransformation process, effected by means of selected microbial strains, for the preparation of 3-O-glycosyl derivatives of colchicinoid compounds.