Quinones are minute yet strong molecules that aids living cells in breathing. These are also important in cellular respiration, because they form the shuttle transfer of electrons to keep energy production chugging along at a steady rate. Microbes also depend on quinones (menaquinone, vitamin K2, and 1,4-dihydroxy-2-naphthoic acid or DHNA) to maintain redox balance and to grow. They can also have direct effect on human health making bone stronger as well as improving the cardiovascular system
Quinones are two edged swords. When in excess, they may result in oxidative stress and cellular damage. In an mBio paper on August 2025, Li et al. demonstrate how a bacterial species of food significance, Lactococcus lactis, maintains a tight balance in the level of quinone by a two-regulator hierarchy and substrate scarcity mechanism
The Dilemma Between Toxicity and Benefit
Quinones then are the spark plugs in fermentation and in growth by micro organisms:
Promote electrons in respiration
Buffer cells against stress by controlling redox balance
Fermented foods that contain high levels of vitamin K2 include cheeses, yogurts and natto
Nevertheless, there is a danger of the backfire of excess quinones. The experiment demonstrates that at excessive levels DHNA, cell growth decreases and it becomes more affected by strong oxidants. Simultaneously, when DHNA concentrations are extremely low, the cell may go without energy or survival derived benefits.
This fine balance has baffled scientists and prevented attempts to produce microbes that make more vitamin K2 to be used nutritionally.
The Study: How L. lactis Regulates Quinones
The researchers explored the biosynthesis of DHNA, the key precursor to vitamin K2. Using synthetic biology, biosensors, and mathematical modeling, they mapped out how the bacterium controls DHNA.
Key findings:
Dual Enzyme Regulation
Two enzymes, MenF and MenD, play central roles in regulating DHNA levels.
MenD is especially influential because it can be inhibited by DHNA itself (feedback control).
MenF catalyzes reversible reactions, allowing it to fine-tune the flux of quinone production.
Substrate Limitation
The supply of chorismate, the starting material for DHNA, sets a natural ceiling on how much quinone can be produced.
This ensures that DHNA never reaches toxic levels inside the cell.
Homeostasis Through Feedback
Even when scientists tried to overexpress these enzymes, DHNA production plateaued, showing that the system resists overproduction.
The balance keeps DHNA levels high enough to benefit growth but not so high that they become harmful.
Why This is Important
This is not just a microbiology curiosity, it implies many things.
Food and Nutrition
Natural vitamin K2 sources are many fermented foods, including dishes prepared with it. K2 benefits bones and cardiovascular health. With the knowledge of how DHNA is regulated, food scientists might be able to modulate microbes to enhance the vitamin K2 concentrations in fermented foods provided the concentrations are not too high.
Metabolic Engineering
In the case of biotechnology, the results provide an insight on why previous methods which involve simply overexpressing enzymes to increase the production of quinone failed to work on a consistent basis. Now, the strategies may work towards:
Variants of hormones of the type Targeting MenD which overcome feedback inhibition
To Overcome natural limits of production of chorismate by increasing its supply
Microbial Health and Adaptation
The paper also demonstrates the adaptive growth of L. lactis to have worked through using DHNA in variable conditions. Optimal levels of DHNA assist cells to breathe better in response to stressful conditions, and at higher levels, it can cut short survival. The resulting integrated control can be an evolutionary mechanism of protection
Evolutionary Perspective
The dual regulatory system portrays the evolutionary trade-off. Microbes acquired those features over which they need to maximize survival, not industrial production. By maintaining a balance of quinone levels, they are maintained at a constant rate so that there is stable growth even in natural settings where excess production could prove fatal.
This reflects the fact that other redox-active compounds such as flavins and phenazines are also closely controlled in bacteria. At the heart of this movement statistically, microbes are programmed to optimize homeostasis above all else.
Future Directions
The research leads to:
The solution has been to engineer DHNA insensitive MenD at the expense of feedback inhibition.
To overcome the natural constraints, it is desirable to increase chorismate synthesis and quinone pathways.
The development of safer industrial food fermentation microbial strains, with a trade-off between nutritional benefits and cellular well-being.
The strategies would help fermented foods become more nutritious and promote the field of microbial biotechnology
Conclusion
This new study throws some light on the delicate balancing act that goes on within microbes: maintaining equilibrium levels of quinones to sustain cellular growth without becoming lethal. Keeping in mind the regulation systems of two enzymes and appreciating the limitation of substrates in microbes now scientists understand why microbes are among the organisms that resist overproduction of vitamin K2 precursors.
This knowledge is priceless to the food industry, and biotechnology, as well as human health. It could clear the path to engineered probiotics, enriched fermented foods, and strategies in metabolic engineering.
The next time you indulge in some cheese, yogurt, or natto, remember hundreds of tiny microbes are running a sophisticated balancing act to insure quinones are kept just right.
Reference
Li, S., Zhang, J., Ajo-Franklin, C. M., & Igoshin, O. A. (2025). The growth benefits and toxicity of quinone biosynthesis are balanced by a dual regulatory mechanism and substrate limitations. mBio. https://doi.org/10.1128/mbio.00887-25