Vitamin K2: Engineering food bacteria for cheaper and greener supplements

New research discovers that the common food bacterium Lactococcus lactis can be engineered to overproduce vitamins, providing a greener and more cost-effective alternative to chemical synthesis or extraction from plants and animals.

The study in mBio uses biosensing, genetic engineering, and mathematical modeling to uncover how substrate availability and genetic architecture impose production limits — and how those limits can be overcome.

Rice University, US, researchers looked at L. lactis, which regulates the production of a key precursor in vitamin K2 biosynthesis. The precursor, 1,4-dihydroxy-2-naphthoic acid (DHNA), is a type of chemical building block that is later transformed into the vitamin, which is linked to benefits in mobility, bone, heart, and women’s health.

“Vitamin-producing microbes could transform nutrition and medicine, but we must first decode their inherent checks and balances,” says co-corresponding author Caroline Ajo-Franklin, the Ralph and Looney professor of Biosciences, director of the Rice Synthetic Biology Institute, and a Cancer Prevention and Research Institute of Texas Scholar. 

“Our work shows how L. lactis finely tunes its internal supply of the K2 precursor, allowing us to rewire it with precision.”

Lower prices and fortified foods

The researchers note that because bacterial cells usually restrict their production to self-sustaining levels, examining the control system can allow for increased production.

First author Siliang Li, a former graduate student and a postdoctoral fellow (Image credit: Rice).Because the precursor is challenging to detect, the team first built a custom biosensor in a different bacterium, which was thousands of times more sensitive than conventional methods and required minimal lab equipment. 

They then used genetic tools to change the enzyme levels in L. lactis’ biosynthetic pathway, measuring output under different conditions.

According to the researchers, L. lactis maintains a balance to avoid toxicity. Overexpressing pathway enzymes did not lead to more output beyond the threshold. 

However, the order of enzyme-encoding genes on DNA influenced precursor levels. Rearranging these genes altered the amount of intermediate the cell produced.

“By tuning substrate supply, enzyme expression, and gene order simultaneously, we can push production above the natural ceiling,” comments first author Siliang Li, a former graduate student and a postdoctoral fellow at Rice University.

Engineering microorganism-fueled bio-factories

The researchers believe this discovery opens paths to engineering L. lactis or other food-grade bacteria to make more vitamin K2 in fermentation processes or probiotic formulations. 

“Enhanced production could reduce the need for feedstocks and lab space, ultimately lowering costs and bringing fortified foods and supplements closer to reality,” adds co-first author Jiangguo Zhang and a Rice graduate student. 

In other advances in bacterial engineering, scientists genetically modified the common gut bacterium Phocaeicola vulgatus. When proliferated in the gut microbiome, it reduced oxalate levels, emerging as a potential treatment for kidney stones.