Streptomyces HS7523 Fermentation for Milbemycin A3 Yield
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The existing production methods for milbemycin A3 face challenges in achieving high yields due to the difficulty in isolating the single component from fermentation broth, where the ratio of milbemycin A3 to A4 is similar, resulting in low A3 content and high impurity levels, limiting its application and industrial production efficiency.
Innovation Solution
A new microbial strain, Streptomyces HS7523, is developed, which increases the yield of milbemycin A3 to over 70% in fermentation broth with a unit yield of more than 3000 ug/ml and low impurity content, achieved through aerobic fermentation in a nutrient medium with specific carbon and nitrogen sources, optimized temperature, and submerged fermentation conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional fermentation methods are used to produce milbemycin, then milbemycin can be obtained as a mixture of A3 and A4 components, but the content of A3 is less than 30% and the separation is difficult
Solution Approach 1:
The patent applies parameter changes by modifying the fermentation conditions including temperature (25-35°C), pH (6.0-8.0), dissolved oxygen (not less than 35%), and nutrient composition to optimize the production of milbemycin A3. These parameter adjustments shift the metabolic pathway to favor A3 synthesis, achieving over 70% A3 content in the fermentation broth.
Solution Approach 2:
The patent employs self-service by using the fermentation broth itself as the production system, where the Streptomyces strain naturally produces the desired A3:A4 ratio under optimized conditions. The system self-regulates the component distribution through controlled fermentation parameters, eliminating the need for complex external separation processes.
2Productivity
If conventional fermentation is used, then milbemycin production can proceed, but the unit yield of A3 is limited and production costs are high
Solution Approach 1:
The patent implements parameter changes by optimizing fermentation temperature (25-35°C), pH (6.0-8.0), dissolved oxygen (not less than 35%), and nutrient composition to maximize A3 production. These changes enable the system to achieve unit yields of A3 greater than 3000 ug/ml with A3 content exceeding 70%, significantly improving productivity and reducing the loss of A4 component.
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 improved yield and purity of milbemycin A3 produced by Streptomyces HS7523 significantly enhance the feasibility of its industrial production, reducing production costs and expanding its application range as a single component.
Implementation Method 1
aerobic fermentation of Streptomyces HS7523 (CGMCC No. 9672) in nutrient medium containing assimilable carbon source and assimilable nitrogen source
Data Source
Figure 1~2B
Figure 3~4
Figure 5~6
AI summary
Provided are a Streptomyces (Streptomyces hygroscopicus) HS7523 and a method for preparing milbemycin A3 by culturing the Streptomyces. The Streptomyces (Streptomyces hygroscopicus) HS7523 is deposited in "China General Microbiological Culture Collection Center" with an accession number of CGMCC No.9672 on September 16, 2014.