“Take your vitamins!”. How many times have you heard the expression? Since their discovery in the first decade of the 20th century, we know that they are an important part of our diet. They are essential nutrients that our body needs to function properly. B1 helps our cells with the metabolism of glucose, amino acids, and lipids. B12 is involved in the metabolism of every cell of the human body and affects DNA synthesis and regulation. Scurvy, beriberi, pellagra, rickets… all these diseases are caused by vitamin deficiency. And we cannot produce most of these molecules ourselves: we have to include them in our diet. For this reason, their demand in any form (supplements and additives) has only grown. Just between 1999 and 2012 the market volume for fermented vitamins increased from 5% to 45%. So, where do all these molecules come from?
Take for example the vitamin B complex. A set of 8 molecules that are essential on our day to day. Their production takes place in separate industrial plants, equipped with industrial reactors. In these reactors, the chemical compounds combine themselves in chain reactions that give birth to the final molecules. These manufacturing processes, while efficient, have some down-sides. The chemical reactors work continuously, so the manufacturing plants must be operated all the time, rising the costs. They also use non-renewable chemicals and produce hazardous waste. So what if we could get our vitamins not from chemical synthesis, but from somewhere else? Synthetic biology can help us develop bacteria that can produce vitamin B. What’s more: some of them are already the commercial option for producing it!
A good example is the bacteria B. subtilis. Roche, the healthcare company, chose a strain of this bacterium to overproduce and secrete B2. Then it is crystalised and treated to obtain a product that is 96% pure. And since this purity is not good enough, recrystalising it yields 99% pure vitamin. As of 2018, only two microorganisms are responsible for the production of all the vitamin B2 worldwide: B. subtilis and A. gossypii. These bioprocesses, when compared with the previous chemical processes, cut down the production costs by a 43%, and reduced the CO2 emissions around 30%!
However, it’s not always that easy. Producing vitamin B12 on an industrial scale took some time. In nature, only a handful of bacteria and archaea produce this essential molecule. So, the best option to manufacture B12 has always been to use the tools that nature gave us. In this case, we have several bacteria to choose from: Pseudomonas denitrificans, Propionibacterium shermanii, or Sinorhizobium meliloti. Sadly, all of them have shortcomings. The fermentation times are long, and there are still no good genetic tools to improve the strains that we are currently using. But there are other options. Thanks to synthetic biology, E. coli —one of the species that we use at Rafts4Biotech— stands out as a good candidate. Researchers took the genes present in Pseudomonas denitrificans that are responsible for overproducing vitamin B12 and incorporated them into E. Coli. While the amount of vitamin B12 per batch that they produce are still low, they managed to bring down the production time needed. And the genetic tool to work with E. Coli is much broader than with other species, which opens multiple possibilities.
These are only two good examples of how bacteria can be tiny manufacturing plants for those compounds that we strive to get. If you are curious about how far we are from producing all the vitamin B complex using only microorganisms, check out our paper and find out!