Breast milk is an extremely complex food matrix for product developers to try to imitate. It changes in composition day by day and even hour by hour and is dependent on what the mother eats, where she is in the lactation cycle and if she is fighting off an infection.
Research shows it also depends on how old the baby is, how many times a day it feeds and even on the amount of mother-baby contact time.
Boston-based biotech company Conagen says that while breast milk will always be best for a baby, packaged infant formula products can nonetheless be improved. It is using synthetic biology to manufacture and scale up some of the most important nutrients in breast milk for new-borns’ development.
“The overall challenge here is really just trying to get babies as healthy as they will be when breast fed,” said the company’s vice president of innovation, Dr Casey Lippmeier. “That’s an impossible task – to be clear, it isn’t something that is actually achievable – but if we can get as close as possible, that’s a clear success.”
Three key ingredients
Conagen is currently working on three ingredients for infant formula: lactoferrin, 2'-fucosyllactose (2'-FL), and phenylalanine-butyramide (FBA).
Human lactoferrin is an iron-binding protein that is linked to several physiological and protective functions, including anti-infective and anti-inflammatory activities. It also regulates iron absorption in the infant gut and has a probiotic effect.
Human milk oligosaccharides (HMOs) are important nutritional compounds only found in breast milk. The most abundant HMO in human milk is 2’-fucosyllactose (2’-FL), which plays a role in promoting a healthy gut microbiome, strengthening the gut barrier function, and suppressing pathogens.
Finally, FBA works by releasing the short-chain fatty acid, butyrate. Butyrate is an important postbiotic and probiotic molecule for building gut health and immunity but has an unpleasant taste that has made it difficult to commercialise as a food ingredient. Conagen’s version is odourless and tasteless.
‘This is where synthetic biology can shine’
Conagen has several production methods for manufacturing these molecules, centred around synthetic biology.
Synthetic biology is allowing companies around the world to produce ingredients that have traditionally been beset with supply chain and scale-up problems in a laboratory. US start-up C16 Biosciences, for instance, uses synthetic biology to produce palm oil without the deforestation while Israel’s Enzymit makes stevia using only the best-tasting rebaudiosides that naturally are found in tiny quantities in the leaf. Cultured Decadence is hoping to make premium protein sources such as lobster more affordable by growing the cells in bioreactors.
Human breast milk clearly fits the bill as a precious resource whose supply is limited.
“This is where synthetic biology can shine,” Lippmeier told Fi Global Insights. “Basically, we go to nature and look for genes, enzymes and biochemical pathways making a given product. We take that information – the genes, enzymes and biochemical pathways – and find way to step them up in bioreactors. That might mean engineering some kind of fermentable microbe that can be grown very robustly or it could be building enzymes devoid of any organism and using those instead to build out our biochemical pathways.”
Conagen produces human lactoferrin via a precision fermentation platform using a proprietary microbe while the HMOs will probably be produced using enzymes in a bioconversion process. For FBA it uses chemical processing techniques rather than synthetic biology.
None of these ingredients is currently available – Conagen is in the process of scaling up production and still has to seek regulatory approval in the US, Europe and other global markets – but it anticipates that the 2’-FL will be on the market within six to 12 months, for instance. The lactoferrin, which is a more complex molecule to produce at scale and still needs to undergo clinical trials, could launch in around two years.
Conagen claims its differentiator over other synthetic biology companies is its host organism collection.
“Most companies in synthetic biology, fermentation and biomanufacturing generally focus on just E. coli and yeast, and they torture the heck out of them to try to make every molecule they can think of,” said Lippmeier. “But the fact of the matter is, there is not one single host that’s best for making every single enzyme or molecule that exists. Our philosophy in terms of host selection is to look at nature and try to find an organism that is already making something as close to the desired molecule as possible.”
Conagen currently has 14 organisms, half of which are proprietary, that have been selected and developed with the help of artificial intelligence. Where possible, it says it uses non-GMO techniques.
A game-changing ingredient
Lippmeier said these ingredients have the potential to be “a big gamechanger” for the infant formula industry.
“I think whatever infant formula company chooses to partner with us first will have a pretty big market advantage. The benefits of these ingredients, at least for the HMOs, are already very clear but there’s more clinical evidence coming out, and as we develop our clinical evidence for FBA and lactoferrin that will add even more to that story.”
Ensuring its ingredients are cost-competitive will be important to ensuring their uptake, he added.
“The ingredients we are talking about would be new to infant formula but, that said, we still want to make it as competitive as possible. We have to keep infant formula affordable because it doesn’t do us good to make all these advancements with the goal of improving infant health if mothers can’t afford it.
“The food industry in general is driven by a lot of these cost challenges so this is another way synthetic biology really shines, it allows us to optimise the yield of all our products so we can meet the cost challenge well above and beyond what nature can provide for us.”
Conagen also plans to continue researching and developing other nutrients in breast milk.
“There’s a gigantic spectrum of things that can go into formula that are not already provided by what is usually the cow-milk base on which infant formula is made. It’s just a matter of getting through that list as quickly as we can,” Lippmeier said.