ARTP-Mutated Milbemycin Strain for High-Yield 3:7 A3:A4 Fermentation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing milbemycin production technologies face challenges such as a complicated process, low fermentation level, and difficulty in achieving the required A3:A4 ratio of 3:7, limiting industrial application and market demand.
Innovation Solution
A strain of Streptomyces hygroscopicus var. aureolacrimosus HZMRYB-5 is developed through atmospheric and room temperature plasma (ARTP) mutation, followed by optimized fermentation conditions, including specific culture media and process parameters, to enhance milbemycin yield and A3:A4 ratio.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional strains are used for milbemycin production, then the production process can be maintained, but the fermentation level is low and the A3:A4 ratio cannot meet market requirements
Solution Approach 1:
The patent applies parameter changes by utilizing atmospheric and room temperature plasma (ARTP) mutation to alter the genetic parameters of the Streptomyces hygroscopicus var. aureolacrimosus strain. This mutation process modifies the strain's metabolic parameters to achieve both high fermentation level and the required A3:A4 ratio of 3:7, resolving the contradiction between productivity and manufacturing precision.
Solution Approach 2:
The patent replaces conventional mechanical breeding methods with atmospheric and room temperature plasma (ARTP) mutation technology. This substitution enables more precise control over strain characteristics, allowing simultaneous optimization of fermentation level and A3:A4 ratio without the limitations of traditional mechanical selection processes.
2Manufacturing precision
If multiple strains are screened and fermented to achieve appropriate A3:A4 ratio, then market requirements can be met, but the production process becomes more complex and time-consuming
Solution Approach 1:
The patent applies preliminary action by performing ARTP mutation on the Streptomyces hygroscopicus var. aureolacrimosus strain before fermentation to directly obtain a strain with the desired A3:A4 ratio of 3:7. This preliminary genetic modification eliminates the need for subsequent complex separation, purification, and mixing operations, thereby reducing production process complexity while maintaining manufacturing precision.
3Productivity
If conventional fermentation processes are used, then production can be maintained, but the fermentation yield is insufficient for industrial requirements
Solution Approach 1:
The patent applies parameter changes by optimizing fermentation parameters including temperature (28-30°C), pH (7.0-7.5), aeration rate (0.5-2.0 vvm), and agitation speed (100-500 rpm) to achieve high fermentation yield. The ARTP-mutated strain HZMRYB-5 exhibits enhanced metabolic parameters that consistently produce high yields of milbemycin A3 and A4, ensuring both high productivity and production 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
The strain HZMRYB-5 achieves a 70% improvement in fermentation yield and 35% increase in fermentation level, meeting industrial requirements and reducing production costs, while achieving a nearly 3:7 A3:A4 ratio in the fermentation liquid.
Implementation Method 1
the original strain is subjected to mutation breeding by an atmospheric and room temperature plasma (ARTP) mutation
Implementation Method 2
Milbemycin is a secondary metabolite obtained by deep liquid fermentation of Streptomyces milbemycinicus
Data Source
AI summary
A strain for high-yield production of milbemycin and use thereof is disclosed. In the present invention, an original strain MI-W1-2017001 is subjected to mutation breeding by an atmospheric and room temperature plasma mutation method to obtain a high-yield strain HZMRYB-5. The fermentation level of the strain is improved by about 70% compared with the original strain, and the fermentation level is further improved by about 35% through optimization of a fermentation process and a formulation, so that the fermentation cost of the product is further reduced, and requirements for the industrial fermentation level are met. On the basis of optimizing the fermentation process, the ratio of A3 and A4 in a fermentation liquid is nearly 3:7 through mixed fermentation of the strain MI-W1-2017001 and the strain HZMRYB-5, so that market demands are greatly met, the process steps of separation, purification and then mixing are reduced.