A team from UWA and Chalmers University of Technology recently published groundbreaking research on Lactococcus lactis, a ubiquitous food bacterium. That finding may change the way we manufacture vitamin K₂ —otherwise known as menaquinone. On August 11, the journal mBio released a revolutionary study. It shows for the first time how this bacterium regulates the production of a critical precursor necessary for the production of vitamin K₂. By better understanding this regulation, scientists aim to engineer the bacterium to produce higher yields of the vitamin, potentially making it more affordable and environmentally friendly.
The research team bottom-lined their dynamic approach to their study. Through biosensing, genetic engineering, and mathematical modeling, they explored how L. lactis balances its internal vitamin K₂ precursor levels. The bacterium walks a tightrope between too much and too little precursor—enough to feed the factory, not so much that it poisons the factory. L. lactis artfully fine-tunes its biosynthetic pathway via a TCS regulatory cascade. That degree of precision may be key in fermentation processes down the line, as well as to the development of future probiotic formulations.
Insights from the Research Team
First author of the study and former graduate student Siliang Li said their findings were important. He stated, “By tuning substrate supply, enzyme expression, and gene order simultaneously, we can push production above the natural ceiling.” This claim emphasizes the possibility for scaling up vitamin K₂ production using specialized strains of L. lactis.
Co-first author Jiangguo Zhang, a Rice graduate student in Rice’s Department of Electrical and Computer Engineering, echoed this sentiment, emphasizing the larger impacts of increased production. He noted, “Enhanced production could reduce the need for feedstocks and lab space, ultimately lowering costs and bringing fortified foods and supplements closer to reality.” According to the research, biocontrol L. lactis has real potential to improve nutritional products dramatically.
Co-corresponding authors Oleg Igoshin and Caroline Ajo-Franklin contributed additional context about what the study means for future research. Ajo-Franklin, who is the Ralph and Looney Professor of Biosciences and director of the Rice Synthetic Biology Institute, remarked, “Vitamin-producing microbes could transform nutrition and medicine, but we must first decode their inherent checks and balances.”
Mechanisms of Regulation
This research shows the skills of L. lactis, using an advanced control system to increase or decrease their production of menaquinone precursors. The bacterium’s internal regulation consists of a dual mechanism that mitigates the growth benefits and toxicity of quinone biosynthesis.
Igoshin pointed out, “Once we allowed for depletion of the starting substrate, the model output matched our experimental data.” This powerful observation must remind us that substrate availability is a key limiting factor in regulating production rates. He further noted, “It became clear that cells hit a natural production ceiling when the substrate runs low,” emphasizing the challenges faced in maximizing output without compromising health safety.
Using recently developed genetic tools, the team was able to tweak enzyme levels within L. lactis’ biosynthetic pathways. This adjustment allowed them to get highly detailed control over the timing of precursor introduction. By comparing and testing these pathways, the researchers expect that they will be able to maximize the yield of vitamin K₂.
Future Applications and Implications
The implications of this research go far beyond vitamin production. If successfully engineered for greater output, L. lactis has the potential to be a key player in formulating sustainable, healthful innovations. The muscular efficiency of vitamin K₂ production could mean significant cost savings for fortified foods and dietary supplements.
Ajo-Franklin’s work with vitamin-producing microbes as L. lactis, and understanding the checks and balances within them, she said, has broader implications. These lessons are incredibly important for developing the future of nutrition and medicine. The team’s research is an exciting advance in the ongoing quest to leverage microbial power to tackle global nutritional challenges.