Optimisation of organic selenium production using Saccharomyces cerevisiae
Abstract
The company required a selenium containing yeast product for the animal feed industry
having both a high selenium content and also a high selenomethionine content. The
selenium content was set at a minimum of 2,000 ppm and the selenomethionine content
at 62.6% +/- 4%. The research department was also investigating the medical benefits of
selenium yeast and had a requirement for a product with a high selenoprotein content.
The medical benefits of selenium compounds are well documented, Schwarz and Foltz
(1957) discovered that selenium could protect Vitamin E deficient rats from liver necrosis
(Schwarz and Foltz, 1957). Tobe et al. (2017) demonstrated the antioxidant effects of
selenoenzymes in cancer prevention (Tobe et al., 2017). Zare et al. (2017) highlighted
the importance of the selenium containing enzyme glutathione peroxidase in protecting
cells from oxidative damage by free radicals (Zare et al., 2017). Lippman et al. (2009)
indicated in their research that selenium and Vitamin E or their combination could reduce
the occurrence of prostate cancer (Lippman et al., 2009). Lovell et al. (2009) used the
company’s product in a study investigating the oxidative damage in a transgenic mouse
model of Aß. Aß is an amyloid ß-peptide which may play a critical role in the oxidative
damage associated with Alzheimer disease. They found that supplementation with the
selenium product decreased oxidative damage to RNA and DNA in the mice (Lovell et
al., 2009). This suggested that selenium could be a neuro-protective agent in preventing
Alzheimer disease. The company has used significant resources in this research area, a
suitable selenium product was important for their work. The company decided to develop
a product that would delay the onset of Alzeimer disease and clinical trials were
undertaken in the U.S. using the available product. As part of these trials in accordance
with FDA protocols, there was a requirement for a product of consistent and reproducible
quality that could be produced on an ongoing basis. These requirements were the
catalysts for the present work.
The target of obtaining a product with 2,000 ppm minimum selenium concentration was
achieved, but producing a product with 62.6% +/- 4% was problematic. The production
batches (Details in Section 2.8) were reviewed and an assessment was made of the best
batches. Seven batches were then produced based on what was perceived to be the
optimum parameters settings. The results were not as good as expected and fifty three
batches were subsequently produced in the pilot plant. The production parameters were then subjected to statistical and response surface methodology analysis with a view to
optimising selenium incorporation and increasing the selenomethionine content of the
yeast. The results of this suggested that it was important to raise the pH, increase the
ammonia addition and use a low phosphate addition. These findings were verified in a
confirmation batch. The company has progressed this project over the years and is now
at stage two clinical trials.