A new study has revealed how a widely used food bacterium manages its internal chemistry to survive and thrive. The discovery could pave the way for greener, cheaper vitamin production for food and health industries.
Vitamin K₂, or menaquinone, plays a key role in bone health, blood clotting and cardiovascular function. It is produced naturally by certain bacteria, including Lactococcus lactis, a staple of dairy fermentation.
This microbe generates an unstable intermediate compound essential to all forms of vitamin K₂. But it makes only enough to support its own growth, preventing a toxic buildup.
This natural self-limiting system poses a challenge to those trying to engineer bacteria to produce more vitamins. Microbes tend to cap production at self-sustaining levels, slowing commercial applications.
Engineering them to make extra vitamins could replace energy-intensive chemical synthesis or plant extraction, but scientists must first understand the production “brakes” built into their biology.
“Vitamin-producing microbes could transform nutrition and medicine, but we must first decode their inherent checks and balances,” said Caroline Ajo-Franklin, co-corresponding author of the study and director of the Rice Synthetic Biology Institute.
She said their work shows how L. lactis fine-tunes its supply, creating an opening for precision genetic rewiring.
Tracking hard-to-detect compound
The research team combined biosensing, genetic engineering, and mathematical modelling to study the process.
Because the vitamin K₂ precursor is difficult to measure, they built a highly sensitive biosensor in a different bacterium. The device is thousands of times more sensitive than conventional tools and requires little lab equipment.
Researchers then altered enzyme levels in the vitamin’s biosynthetic pathway and measured output under different conditions. These results fed into a mathematical model. At first, the model assumed an unlimited supply of starting material, but the predictions did not match lab results.
“Once we allowed for depletion of the starting substrate, the model output matched our experimental data,” said Oleg Igoshin, co-corresponding author. It became clear that production hit a ceiling when the substrate ran low, like trying to bake more cookies with extra trays but without enough flour.
Gene order shapes production limits
The team found another control layer in the order of enzyme-encoding genes on DNA. Rearranging these genes changed how much of the intermediate compound the cells produced.
This suggests an evolutionary mechanism that controls production in ways not fully understood before.
“By tuning substrate supply, enzyme expression and gene order simultaneously, we can push production above the natural ceiling,” said first author Siliang Li, now a postdoctoral fellow at Rice.
Boosting L. lactis output could enable more efficient fermentation processes and even probiotic supplements that deliver higher vitamin K₂ doses.
Co-first author Jiangguo Zhang said greater efficiency could reduce feedstock needs and lab space, lowering costs for fortified foods and supplements.
The study, published in mBio, was supported by the Cancer Prevention and Research Institute of Texas and the National Science Foundation.