Biotransformation Technologies

Figure 1: steroid Hormones

Popular biotransformations throughout history

have included utilising yeast to convert glucose to ethanol and CO2, the use of lactic acid bacteria to make yoghurt and the employment of the fungusAspergillus niger to make citric acid. More recent biotransformation technologies, however, have become more sophisticated, involving such procedures as the production of pharmaceuticals and the development of methods to reduce environmental pollution.

Biotransformation Technology in the Production of Steroid Hormones

Steroid hormones ( fig.1) are important therapeutic drugs, as they assist in various metabolic functions in the human body. Manufacturing these chemicals involves many steps and the costs involved can be exorbitant. Recent use of micro fungi and bacteria to carry out some of these steps has proved to be extremely efficient and cost effective.

Examples include using the fungus Rhizopus arrhizus to convert progesterone to 11- hydroxy progesterone and finally to cortisone (fig.2), which is an antiarthritic drug. In this process, progesterone is added to a fermentation tank containing the fungus, which hydroxylates the progesterone at the number 11 carbon atom in its steroid ring.

Such a hydroxylation step would otherwise be laborious and expensive using synthetic methods alone. Further chemical synthesis steps are then used to convert 11-hydroxy progesterone into cortisone. The incorporation of biotransformation technology into this process has reduced the cost of cortisone production in the U.S. by a factor of around 400.

Researchers at the Tehran University of Medical Sciences have also investigated the biotransformation properties of the fungus Nerospora crassa, which can transform the steroid hydrocortisone into a pregnane and androstane derivative by removing the hydroxyl side chains from the molecule. This has commercial potential, as drugs in this family are used to treat endometriosis and other hormonal conditions, and can also act as anti-inflammatory agents.

Biotransformation in the Production of Antibiotics and Vitamin C

Biotransformation technologies are not limited to the production of steroid derivatives. New, more effective antibiotics, for instance, can be manufactured from existing ones using microbe-mediated transformations. Examples of this include penicillin and cephalosporins, which can be deacylated by microbes to produce semi-synthetic varieties of the original antibiotics.

In addition, the bacterium Acetobacter suboxydans can be used in the production of ascorbic acid (vitamin C), by transforming D-sorbitol, a derivative of glucose, to L-sorbose. L-sorbose is then chemically transformed to ascorbic acid.

Biotransformation and the Environment

A study by Lai, Scrimshaw and Lester (2002), has found that the algaChlorella vulgaris, can transform both natural and synthetic oestrogens. The syntheric oestrogen, oestradiol valerate, was shown to be transformed to oestradiol, and the natural oestrogens oestradiol and oestrone were also converted to related compounds in the presence of the alga.

This has environmental significance, as it throws light on the ability of microbes to detoxify various pollutants present in sewage and other runoff. Indeed, some macroalgae have been nicknamed ‘green liver’, as they have similar detoxifying enzymes as the human liver. Other algal species are capable of transforming heavy metal and organic pollutants.

Perhaps one of the more significant recent discoveries in this area has been that of the hydrocarbonoclastic bacteria, which can degrade alkanes as part of their metabolism. This shows potential for the possible biodegradation of oil spills in marine environments. Scientists looking for ways to reduce the recent Deepwater Horizon oil leak are suggesting that naturally occurring bacteria from the Vibrio family are capable of degrading some of the oil.

They are already adding fertiliser to the oil that has reached the shore to promote the growth of these microbes. The introduction of additional oil eating bacteria such as Alcanovirax borkumensis is also being considered.

Other examples of such ‘bioremediation’ include using microbes to detoxify compounds present in pesticides and raw sewage in both soil and water ecosystems. The US Geological Survey (USGS), for instance, has been researching the biotransforming effects of microbes such as the bacterium Dehalococcoides ethenogenes on chloroethenes, common contaminants of groundwater systems. These microbes are able to convert chloroethanes to safer,less chlorinated compounds.

Biotransformation Companies and the Future

The Biotech company, Spi Bio is an example of the commercial application of biotransformation technologies. This organisation advertises services that include the production of metabolites by bacteria, filamentous fungi and yeasts, which mimic the chemical pathways present in the mammalian cytochrome system.

Biotransformation technologies have obviously come a long way since the early use of yeasts and bacteria to make bread, wine and yoghurt. With the millions of species of bacteria and fungi on the earth the possibilities for utilising their biochemical pathways to our own advantage are virtually endless.

References

Fathabad, Yahzdi, Faramarzi, and Amini, 2006, ‘Biotransformation of Hydrocortisone by Neurospora crassa’ Journal of Sciences, University of Tehran, sid.ir, accessed 4/6/2010

Lai, Scrimshaw and Lester, 2001, 'Biotransformation and Bioconcentration of Steroid Estrogens by Chlorella vulgaris', Imperial College of Science, Technology and Medicine, London, asm.org, accessed 3/6/2010

SPI BIO Bertin Group, 'Generating New Chemical Entities Using Biotransformation Technology' spibio.com, accessed 4/6/2010

Figure 2: Cortisone

USGS, 2008, Microbial Degradation of Chloroethenes in Groundwater systems, toxics.usgs.gov, accessed 2/6/2010