Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis

Area of Science:

• Microbial Biotechnology
• Biochemistry
• Molecular Biology

Background:

• Microbial synthesis offers a sustainable alternative to plant extraction or chemical synthesis for producing valuable polyphenols.
• Polyphenols, such as resveratrol, can be cytotoxic to microorganisms, hindering their efficient production.
• Strategies are needed to overcome the detrimental effects of polyphenols on microbial cell integrity and production.

Purpose of the Study:

• To investigate the cytotoxic effects of resveratrol accumulation in the cell membrane and cell wall of Corynebacterium glutamicum.
• To identify methods to mitigate resveratrol's detrimental effects and enhance its microbial production.
• To explore the potential of free fatty acid supplementation as a strategy to improve microbial polyphenol production.

Main Methods:

• Utilized Corynebacterium glutamicum for microbial synthesis of resveratrol.
• Employed experimental methods and molecular dynamics simulations to study resveratrol's effect on cell membranes.
• Screened various free fatty acid supplements to identify those that alleviate resveratrol's cytotoxicity.

Main Results:

• Resveratrol accumulation was found to rigidify the cell membrane of Corynebacterium glutamicum.
• Palmitelaidic acid and linoleic acid were identified as effective supplements to counteract resveratrol's cytotoxic effects.
• Supplementation with these fatty acids resulted in a threefold increase in the final resveratrol titer.

Conclusions:

• Free fatty acid supplementation is a cost-effective approach to enhance microbial production of resveratrol by mitigating membrane damage.
• This strategy is transferable to the microbial production of other membrane-active bioproducts and polyphenols.
• Targeting membrane effects represents a viable engineering strategy for improving microbial cell factories.