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11 July 2022 | Story Andre Damons | Photo Supplied
Prof Martie Smith and Prof Drik Opperman
Prof Martie Smit and Prof Dirk Opperman in the Department of Microbiology and Biochemistry filed a patent entitled “Process for the chemical modification of alkanes, fatty acids and fatty alcohols”.

Flavours and fragrances have a wide application in the food, feed, cosmetic, chemical and pharmaceutical sectors. Many flavour compounds are still produced via chemical synthesis or via extraction from plant or animal sources. However, there is increasing interest in their bio-production or the use of flavour compounds of (micro) biological origin. 

One reason for this shift is that chemical synthesis often uses environmentally unfriendly processes. Chemical synthesis usually also produces racemic mixtures with the second enantiomer, mirror image of the looked-for compound, often having undesirable organoleptic properties. Furthermore, the consumer has developed a “chemophobia”-attitude towards synthetic chemical compounds, especially when related to food and home-care products.  This applies even to nature-identical compounds – products that occur in nature but are produced via a non-natural chemical process. Products produced with the use of enzymes or microbes from “natural” substrates can be labelled “natural”. The flavour and fragrance industry thus pay higher prices for such products labelled as “natural”.  

The invention

A University of the Free State (UFS) team, led by Prof Martie Smit and Prof Dirk Opperman in the Department of Microbiology and Biochemistry are conducting exciting research in this area. They filed a patent entitled “Process for the chemical modification of alkanes, fatty acids and fatty alcohols”.  

The invention relates to a process for the enzymatic in-chain hydroxylation of C12 to C16 fatty acids, alcohols, and alkanes. Hydroxylation of C12 fatty acid and alcohol provides routes for the synthesis of “natural” δ-dodecalactone. The advantage of these routes is that they do not rely on massoia lactones. Massoia lactones are derived from the bark of Massoia trees which grow in Indonesia. Harvesting of the bark kills the trees.  

The cytochrome P450 enzymes (P450s) claimed in this patent are to the inventors’ knowledge the most regioselective enzymes described thus far that can be used for the synthesis of δ-dodecalactone from lauric acid or 1-dodecanol. The approach that the technology takes is to claim cytochrome P450 enzymes that share 70 % amino acid identity to a set of selected P450s for the regioselective hydroxylation of lauric acid and 1-dodecanol to synthesise δ-dodecalactone.

Still in early stage

The current state of development is early stage with the technology only demonstrated in the laboratory on a small scale (100-200 ml). Before the technology can be commercialised the team would need to further improve the regioselectivity and stability of the P450s and proof that the reactions can be scaled up in bioreactors. The technology will probably be delivered as an enzyme (amino acid sequence) with the desired properties. 

There are other research groups working on a synthetic biology approach for the de novo synthesis of δ-dodecalactone from glucose by genetically engineered microbes. It is still unclear how such a process will compare in terms of product yields, economics and environmental impact with the processes proposed by the UFS patent.

If the team had to partner with a commercial company, their first choice would be to work with an established flavour and fragrance company. Another possibility would be the small French flavour and fragrance company that Dr Alizé Pennec, the post-doc and co-inventor who initially discovered the unique P450 activity, is working for.

Please view the videos for more information on patents.

The Vice-Rector: Research and Internationalisation has released two new calls for applications for funding. Academic staff and researchers are encouraged to submit applications for these funds. At this stage we are not accepting projects from Research Fellows. 

The two funds are: 

1.  The Industrial Engagement Fund 
2.  The Intellectual Property Commercialisation Fund

Each fund has its own guidelines and application process. The guidelines are attached. The applications must be filled in on RIMS.

The RIMS application forms can be found through this link

For more information please click the documents below:



News Archive

Cardiology Unit involved in evaluation of drug for rare genetic disease
2013-01-04

Front from the left, are: Marinda Karsten (study coordinator and registered nurse),
Laumarie de Wet (clinical technologist), Charmaine Krahenbuhl (study coordinator and radiographer),
Lorinda de Meyer (administrator), Andonia Page (study coordinator and enrolled nurse);
back Dr Gideon Visagie (sub investigator), Dr Derick Aucamp (sub investigagtor),
Prof. Hennie Theron, (principal investigator) and Dr Wilhelm Herbst (sub investigator).
Photo: Supplied
09 January 2013


The Cardiology Research Unit at the University of the Free State (UFS) contributed largely to the evaluation of the drug Juxtapid (lomitapide), which was developed by the Aegerion pharmaceutical company and approved by the FDA (Federal Drug Administration). Together with countries such as die USA, Canada and Italy, the UFS’ Unit recruited and evaluated the most patients (5 of 29) for the study since 2008.  

The drug was evaluated in persons with so-called familial homozygous hypercholesterolemia (HoFH).  

Following its approval by the FDA, Juxtapid is now a new treatment option for patients suffering from HoFH. The drug operates in a unique way which brings about dramatic improvements in cholesterol counts.  

According to Prof. Hennie Theron, Associate Professor in the Department of Cardiology at the UFS and Head of the Cardiology Contract Research Unit, HoFH is a serious, rare genetic disease which affects the function of the receptor responsible for the removal of low-density lipoprotein cholesterol (LDL-C) (“bad” cholesterol) from the body. Damage to the LDL receptor function leads to extremely high levels of blood cholesterol. HoFH patients often develop premature and progressive atherosclerosis, which is a narrowing or blockage of the arteries.  

“HoFH is a genetically transmitted disease and the most severe form of hypercholesterolemia. Patients often need a coronary artery bypass or/and aortic valve replacement before the age of 20. Mortality is extremely high and death often occurs before the third decade of life. Existing conventional cholesterol-lowering medication is unsuccessful in achieving normal target cholesterol values in this group of patients.  

“The only modality for treatment is plasmapheresis (similar to dialysis in patients with renal failure). Even with this type of therapy the results are relatively unsatisfactory because it is very expensive and the plasmapheresis has to be performed on a regular basis.  

“The drug Juxtapid, as currently evaluated, has led to a dramatic reduction in cholesterol values and normal values were achieved in several people. No existing drug is nearly as effective.  

“The drug represents a breakthrough in the treatment of familial homozygous hypercholesterolemia. The fact that it has been approved by the FDA, gives further impetus to the findings,” says Prof. Theron.  

In future further evaluation will be performed in other forms of hypocholesterolemia.  

According to Prof. Theron, the findings of the study, as well as the recent successful FDA evaluation, once again confirms the fact that the UFS’ Cardiology Contract Research Unit is doing outstanding work.  

Since its inception in 1992, the Unit has already been involved in more than 60 multi-centre, international phase 2 and 3 drug studies. Several of these studies, including the abovementioned study, really affected the way in which cardiology functions.  

The UFS’ Cardiology Contract Research Unit is being recognised nationally and internationally for its high quality of work and is constantly approached for their involvement in new studies.  

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