Engineered Bacillus Subtilis Strains for Low-Cytotoxicity Mycosubtilins
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Solution Overview
Problem
There is a need for antifungal molecules with improved properties to meet the growing global food demand while reducing the use of chemical inputs and addressing health and environmental impacts, and existing mycosubtilins are not sufficiently effective or safe for large-scale industrial use.
Innovation Solution
Development of genetically modified Bacillus subtilis strains producing new mycosubtilin isoforms, specifically Gln1-C16 and Gln1-C17, with enhanced antifungal activity and reduced cytotoxicity, achieved through mutations in key genes such as resE_I, rpoC, addB, araA, cotY, and 03427/03457, and optimized promoter regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing mycosubtilins are used for antifungal applications, then antifungal activity is achieved, but cytotoxicity increases and safety is reduced
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of mycosubtilin through genetic mutations in the B. subtilis strain. Specifically, mutations in genes encoding lipopeptide synthetases alter the fatty acid chain length and composition of the mycosubtilin isoforms produced, thereby changing the molecular parameters to achieve reduced cytotoxicity while maintaining antifungal activity. The new isoforms produced have C16 and C17 fatty acid chains with specific structural modifications that improve the safety profile.
2Productivity
If chemical inputs are increased to meet growing food demand, then crop yields improve, but health and environmental impacts worsen
Solution Approach 1:
The patent addresses this contradiction by developing biopesticides with modified molecular parameters. The genetically engineered B. subtilis strain produces mycosubtilin isoforms with altered fatty acid compositions (C16 and C17 chains) that enhance effectiveness against plant pathogens, allowing for reduced application rates and lower environmental impact while maintaining or improving crop protection efficacy and yields.
3Reliability
If new mycosubtilin isoforms are produced through genetic modification, then antifungal activity and safety are improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by targeting specific genes involved in mycosubtilin biosynthesis for modification. Rather than attempting comprehensive genome engineering, the invention focuses on mutating key genes (such as those encoding lipopeptide synthetases) that directly control the structural features of mycosubtilin. This segmented approach to genetic modification simplifies the overall process by concentrating efforts on critical pathway genes.
Solution Approach 2:
The genetically modified B. subtilis strain produces the modified mycosubtilin isoforms through its natural metabolic pathways. The cell's own biosynthetic machinery, once directed by the mutated genes, automatically generates the desired C16 and C17 isoforms with reduced cytotoxicity. This self-service approach eliminates the need for complex external production systems or purification processes.
Data Source
AI summary
The present disclosure relates to the field of molecules of antifungal biosurfactants of bacterial origin. More particularly, the present disclosure relates to new Bacillus Subtilis strains producing new isoforms of mycosubtilins, a preparation method therefor, and compositions containing same. These novel mycosubtilin isoforms exhibit improved antifungal activities and reduced cytotoxic properties compared with mycosubtilins of the prior art.