Researchers have decoded the genome of tacrolimus, a drug given after transplants

CGP/DICYT The Instituto de Biotecnología de León (Inbiotec), a Spanish biotechnology institute, has published in Journal of Bacteriology the nucleotide sequence of the genome of the organism producing immunosuppressant Tacrolimus, the leading drug currently used to maintain transplanted organs such as livers, kidneys and hearts. The publication of the genome of Streptomyces tsukubaensis, Tacrolimus-producing bacterium, has been useful to get ahead of other international teams (British, Slovenian and Korean) pursuing the same objective.

This article principally signed by Carlos Barreiro, is the result of a four-year work by a team of 14 researchers (computer specialists, biologists and biochemists) in several countries (the United States, the United Kingdom and Germany, for instance).

Streptomyces tsukubaensis genome sequencing by Inbiotec is a major breakthrough for science, because it is the first genome from a microorganism producing an immunosuppressive compound. As we were told by Barreiro, at present time, it is a molecule of great interest as American and European patents have been overtaken and generic drugs from these organisms are being developed. “Many companies want to develop generic drugs, so a few more teams are attempting to sequence its genome”, he explains.

In this regard, the practical application of the decoded genome will allow to increase the quantity currently produced, because scientists would be able to know biosynthetic pathways involved in its formation process. It will also allow to improve the production process, because other by-products (pollutants) that make Tracolimus purification more expensive, would be removed; and finally, to improve the compound’s application, being able to design more active and soluble forms of the molecule from the organism itself.

“Findings are interesting for several reasons”, as we were told by the researcher, who highlights the fact that even if the molecule was known and was been produced, very little was known regarding the organism producing it. “Thanks to the genome sequencing, we will be able to produce larger amounts and to remove pollutants since one of the issues with Tracolimus is that it is generally mixed with other immunusuppressants and if we are to remove them, we will save a lot of money if we are able to inactivate the genes producing them,” he adds.

Similarly, he adds, “Tracolimus is not excessively soluble, so if the molecule can be genetically modified to be more active or more soluble, we could save al lot of money from purifications and solubilities, and it would be easier to give therapies”. All this, he concludes, “cannot be carried out if the genetics of the organism remains unknown”, a problem solved by Inbiotec’s team.

Tacrolimus Use

Tracolimus, licensed by the FDA in 1993 to be used in humans, yielded benefits of $ 2,340 million in 2011 with different names in the market ( Prograf, Modigraf, Advagraf, etc.).

Tracolimus is also used as an ointment (Protopic) to treat atopic dermatitis in humans and dry eye syndrome in animals. Other applications in autoimmune diseases such as rheumatoid arthritis, ulcerative colitis or Crohn’s disease are also being developed.

Studies with Tracolimus were carried out by Inbiotec’s former director, Dr. Juan Francisco Martín, and were continued by the current management team resulting in collaborations with companies, two doctoral thesis and several papers published in high-impact international scientific journals.