Adaptive Evolution Identifies MHY1-Mediated Transcriptional Reprogramming for Polyphenol Tolerance in Yarrowia...

Area of Science:

• Microbiology
• Molecular Biology
• Biotechnology

Background:

• Polyphenols are widely used bioactive compounds with applications in food, beverages, cosmetics, and medicine.
• Understanding polyphenol toxicity mechanisms and microbial tolerance strategies is crucial due to their expanding use.

Purpose of the Study:

• To investigate adaptive laboratory evolution for polyphenol tolerance in Yarrowia lipolytica.
• To identify genetic mechanisms and adaptive strategies conferring tolerance to distinct polyphenols.

Main Methods:

• Adaptive laboratory evolution of Yarrowia lipolytica to curcumin, naringenin, and resveratrol.
• Whole-genome resequencing to identify mutations and genomic alterations in evolved strains.
• Functional reconstruction of mutations (gene deletion, point mutations) to validate tolerance mechanisms.
• Transcriptomic analysis to understand regulatory changes associated with tolerance.

Main Results:

• Recurrent loss-of-function mutations in the MHY1 gene were identified as a major adaptation conferring broad polyphenol tolerance.
• Resveratrol-evolved strains showed tolerance via chromosome-scale copy-number variation, independent of MHY1 mutations.
• MHY1 inactivation (gene deletion or point mutations) was sufficient to confer high-level tolerance across different polyphenols.
• MHY1 inactivation led to reduced stress-associated pathways and stabilized core metabolic functions.

Conclusions:

• Loss-of-function of MHY1 is a dominant and transferable mechanism for microbial polyphenol tolerance.
• Genome-level adaptations, such as copy-number variation, represent alternative compound-specific adaptive routes.
• This study elucidates key genetic and regulatory mechanisms underlying microbial adaptation to chemical stress from polyphenols.