Designer Bacteria Could One Day Make Cheese Without Milk

Many childhood mornings start with a hefty bowl of crunchy cereal and milk. From glass bottles dropped on doorsteps to gallon jugs in grocery stores, milk is a staple worldwide for its rich taste and nutritious value.

The protein casein is a big contributor to milk’s appeal. It is also sold as a sports supplement, widely used in pharmaceuticals, and is a key ingredient in cheese. The global casein market was valued at $3 billion in 2025 and is projected to nearly double by 2035.

But alongside growing demand, dairy farming contributes to greenhouse-gas emissions, and unsustainable farming practices can damage prairies, wetlands, and forests. Large-scale milking operations also raise ethical concerns for the animals’ well-being.

A new study from scientists in the Netherlands and Denmark suggests an alternative. The researchers engineered Escherichia coli bacteria to make fully functional casein proteins. Like their natural counterparts, the proteins dynamically curled into shapes that grabbed onto calcium—suggesting the artificial milk proteins could boost calcium levels in the body.

“Traditional dairy farming is under pressure to reduce its environmental footprint, particularly regarding methane emissions, water use, and land consumption,” wrote the team. Engineered bacteria to produce casein “offers a promising alternative.”

Microbe Factories

Eating milk protein made by microbes may sound weird, but bacteria are highly efficient chemical factories that can make a large range of products. From insulin to human growth hormone and immune-regulating molecules, bacteria have been a biotech cornerstone. Gene editing tools, such as CRISPR, have further broadened their ability to make medication. Scientists can insert genes to pump out chemicals for cancer-fighting drugs and aspirin. And they have redesigned other microbes to pump out food enzymes and antimalaria drugs.

There has also been success engineering milk proteins, of which the two main ones are whey and casein. These may sound familiar as they’re often sold as protein supplements. Thanks to genetically engineered microbes, it’s now possible to make “whey proteins through precision fermentation, with these proteins now marketed at a premium,” wrote the authors.

But casein is much harder to create in bacteria or yeast. These proteins self-assemble into micelles—large protein clusters that are suspended in milk. The surface of each blob is dotted with phosphate groups acting like tiny grippers that grab onto calcium.

These chemical hotspots are essential to the delivery of calcium in the body. Chug a casein shake, and it will release calcium into the gut where the mineral can be absorbed. Affordable access to casein could help the lactose intolerant reap its benefits for bone health and be a source of protein to those who struggle to find enough of it in their diets.

A Molecular Code

Caseins require some modifications to carry their calcium cargo. Imagine the protein as a wiggly chain of Mardi Gras beads. For the protein to work, some beads must carry phosphate “tags.”

Adding a tag requires a host protein that’s alien to E. coli. Yeast cells, which are more like our cells, should theoretically be better at the task. But this similarity is a double-edged sword: They can also attach other chemical tags not found in casein, potentially ruining the protein. Some yeast enzymes also destroy engineered proteins—not great for wobbly ones like casein.

The new study tiptoed around these landmines. First, the team added genes for three enzymes from a different microbe to create phosphate tags that were better at grabbing casein. Dialing these in took some trial and error, but in the end, the new system worked. They also modified the casein protein itself to mimic its natural counterpart’s ability to carry calcium.

Of course, engineered casein has to be digested as usual. They tested this in a range of simulated digestive fluids, from saliva to those from the stomach and intestines. The engineered proteins were completely digested, suggesting they’re relatively safe.

Dairy-Free World?

To be clear, the study didn’t test whether the bacteria-made casein agreed with people. But the manufacturing process is similar to how insulin and other proteins are produced in E. coli. Engineering casein-producing microbes “offers a promising alternative by reducing reliance on livestock while maintaining the functional properties necessary for dairy applications,” the team wrote.

The results are still a proof of concept. To be commercially feasible, the method would have to be scaled up. But studies already suggest genetically engineered E. coli can produce designer proteins in commercially viable amounts, wrote the team. Other microbes could boost production more. And as the main component in cheesemaking, bacteria-made casein may one day become a dairy-free alternative for cheeses with tantalizing textures and flavors.

For now, the approach lays out a path for other studies trying to harness casein-producing microbes for food and also sustainable adhesives, paints, and fire-resistant coatings.