Echinocandin B Deoxidation Biosynthesis With Fewer Impurities
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Solution Overview
Problem
Current methods for preparing echinocandin B deoxidation analogues suffer from low conversion efficiency, high purification costs, and the presence of complex components and by-products, making them unsuitable for industrialization, while existing chemical and biosynthesis methods use harmful reagents and require pure products.
Innovation Solution
A biosynthetic method using genetically engineered Aspergillus nidulans strains expressing echinocandin biosynthetic gene clusters, such as ecdA, ecdI, ecdK, and htyE, to produce echinocandin B deoxidation analogues with high conversion efficiency and fewer impurities, facilitating industrial-scale production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If chemical synthesis methods are used to prepare echinocandin B deoxidation analogues, then the conversion process can be performed, but the conversion efficiency is low and the cost is high
Solution Approach 1:
The patent replaces chemical synthesis methods with biological synthesis methods using genetically engineered microorganisms. The microorganisms express echinocandin biosynthetic gene clusters to naturally produce the deoxidation analogues, substituting chemical reactions with biological processes that occur in living cells, thereby improving conversion efficiency and reducing manufacturing costs.
Solution Approach 2:
The genetically engineered microorganisms serve as self-contained factories that automatically convert precursor molecules into echinocandin B deoxidation analogues through their metabolic pathways. The cells utilize their own enzymatic systems to perform the synthesis, eliminating the need for external chemical reagents and complex purification processes.
2Productivity
If chemical synthesis methods are used, then deoxidation analogues can be produced, but harmful reagents are required
Solution Approach 1:
The patent substitutes chemical synthesis pathways with biological pathways occurring within living microorganisms. The biosynthetic process uses enzymatic reactions instead of chemical reagents, eliminating harmful substances while maintaining production capability through the microorganism's natural metabolic functions.
3Productivity
If fermentation culture of customized mutants with oxygenase genes knocked out is used, then deoxidation analogues can be obtained, but the components are very complex and purification cost is high
Solution Approach 1:
The patent extracts and removes the oxygenase genes (ecdG or ecdH) from the echinocandin biosynthetic pathway through genetic knockout. This selective removal prevents the formation of hydroxylated by-products, simplifying the component profile and significantly reducing purification costs while maintaining production capability.
Solution Approach 2:
The patent converts the potential harm of complex components and by-products into a benefit by strategically knocking out specific genes. The genetic modification redirects the metabolic flux toward the desired deoxidation analogues, transforming what would be a purification challenge into a streamlined production process with simplified components.
4Productivity
If existing biosynthesis methods are used, then deoxidation analogues can be produced, but pure products are required as input
Solution Approach 1:
The genetically engineered microorganisms perform in situ synthesis, converting precursor molecules directly into echinocandin B deoxidation analogues within the cellular environment. This self-contained production process eliminates the need for external pure product inputs, as the cells themselves generate the final product through their metabolic pathways.
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 method yields echinocandin B deoxidation analogues with good antifungal activity and improved chemical stability, enabling their development into effective antifungal drugs with simplified purification processes.
Implementation Method 1
fermenting and culturing any of the preceding genetically engineered transformant strains to express the target product
Data Source
AI summary
The present invention relates to an echinocandin compound, and a preparation method therefor and the use thereof. Specifically, disclosed in the present invention are an echinocandin B deoxidation analogue and a biosynthesis method therefor. The echinocandin B deoxidation analogue has a good antifungal activity.