glutamate [ 18]. Many cereals are relatively deficient
in lysine, making purified lysine a vital addition to
animal feed formulations. Engineered Escherichia
coli are used to produce two other key feed amino
acids—threonine and tryptophan. The exception is
methionine, which is also a limiting amino acid in
animal feed, but is currently still produced at large
scale via chemical synthesis, because the racemic
mixture produced through organic chemistry can
be readily converted to the bioavailable L-form via
native enzymes, rendering one of the key benefits of
biotechnological production of bioactives moot.
Improvements in fermentation technology and
genetic tools over the decades have increased the
scale and optimized titers for these important industrial fermentations for the largest volume amino
acids. New tools emerging today in biotechnology
may continue to make these processes more efficient,
cost-effective and sustainable.
Essential Fatty Acids
Two fatty acids are technically vitamins – essential
nutrients not synthesized by the human body and
must be ingested. Linoleic acid and alpha-linoleic
acid are essential poly-unsaturated fatty acids, formerly referred to as vitamin F. Today, several other
such fatty acids are recognized as important components of the diet, particularly the omega- 3 fatty acids
docosahexaenoic acid (DHA) and eicosapentaenoic
These omega- 3 fatty acids have become valuable supplements, particularly for infant nutrition
because of their association with neural and visual
development. Much of the DHA produced industrially is fermented by the non-photosynthetic
dinoflagellate, Crypthecodinium cohnii. The cell’s oil
content after fermentation is over 40%, and 40% of
that total oil is DHA [ 16]. For use in infant formulas, the omega- 6 fatty acid arachidonic acid (ARA)
must also be supplemented to prevent DHA from
being converted into EPA. ARA is also biotechnologically produced in the fungus, Mortierella alpina,
which naturally has a fatty acid content at nearly
80% ARA [ 21].
Producing purified EPA was proven more challenging because no natural sources of EPA-rich oil
as the sole poly-unsaturated fatty acid exist. EPA
was purified from fish oil at high economic and
environmental cost for use in fish feed and medical
applications. A biotechnological route to EPA was
more recently commercialized by DuPont, where the
oleaginous yeast, Yarrowia lipolytica was genetically
engineered to produce oil at 57% EPA. The primary
commercial application of this cultured EPA has
been in fish feed for salmon aquaculture [ 16].
Probiotics and Prebiotics
Beyond what microorganisms can produce
when isolated in large fermenters, there has been
significant recent interest in the value of probiotics and prebiotics in gut health and nutrition. We
collaborate with the microbes living in our bodies
unconsciously, noticing them only when something
goes wrong. Increasingly, we are collaborating with
microbes for nutrition consciously, designing new
strains and new fermentation processes, which
enable the large-scale cultivation of key nutritional
Recently, tremendous interest focused on the
value of probiotics—living microbes with the ability
to be ingested to have an effect on health—and prebiotics—ingredients indigestible by humans, but may
modulate the population of microbes in the gut; for
example, certain oligosaccharides shown to modulate the gut microbiome at a genus level [ 22]. Much
of the promise of the microbiome still remains in the
future, but new tools in genome sequencing, biotechnology and fermentation are enabling powerful new
research and development into key probiotic strains
and valuable prebiotic compounds.
The growth of industrial biotechnology during the
20th century had fundamental impacts in nutrition
and our understanding of biochemistry and physiology. In the 21st century, new biotechnology tools and
techniques will enable new understanding of key
nutritional actives and new perspectives on how we
might collaborate with microbes in the future—as
vital parts of our bodies and our industries.
1. Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L. &
Gordon, J. I. Human nutrition, the gut microbiome and the
immune system. Nature 474, 327–336 (2011).
2. Degnan, P. H., Taga, M. E. & Goodman, A. L. Vitamin B 12 as
a modulator of gut microbial ecology. Cell Metabolism (2014).
doi: 10.1016/ j.cmet.2014.10.002
3. Martens H Barg M Warren D Jah, J. H. Microbial production of
vitamin B 12. Appl Microbiol Biotechnol 58, 275–285 (2002).
4. Sych, J. M., Lacroix, C. & Stevens, M. Vitamin B12–Physiology,
Production and Application. Industrial Biotechnology of … (2016).
5. Kang, Z. et al. Recent advances in microbial production of
d-aminolevulinic acid and vitamin B 12. Biotechnol Adv (2012).
doi: 10.1016/ j.biotechadv.2012.04.003
6. Shetty, R. P. Cultured Ingredients Arrive. Perfumer & flavorist
38, 34–37 (2013).
7. Stahmann, K. P., Revuelta, J. L. & Seulberger, H. Three
biotechnical processes using Ashbya gossypii, Candida
famata, or Bacillus subtilis compete with chemical riboflavin
production. Appl Microbiol Biotechnol 53, 509–516 (2000).