Lysine is an essential amino acid that is used in animal feed. It is produced with the aid of bacteria that feed on sugar, and market demand for the product is high.

In the course of several decades, commercial companies in the US and Japan have developed sugar-based technology for producing lysine, but sugar has become a scarce and therefore expensive input factor, and this is no longer regarded as a good solution.

Huge Market

Lysine consumption is now nearly 700,000 tonnes, more than Norway's current salmon production weighs, and the world market is worth in excess of NOK10 billion.

Production takes place with bacteria in large cultivation tanks that may contain as much as 500 000 litres. Organisms nearing the bottom of the food chain can produce their own lysine, but higher animals such as pigs and chickens, not to mention human beings, lack this ability, and need to have it supplied as a component of their food.

Price is another important factor. The price of lysine has long been determined by the price of soy and sugar. Soy protein contains a relatively large proportion of this important amino acid, and farmers therefore may use soybean meal as a feed ingredient. The price of sugar also plays a certain role because it is sugar that is currently used to nourish the bacteria that produce lysine. The price of lysine is currently around NOK15 per kilo, and lysine producers are forever seeking for cheaper raw materials.

Trygve Brautaset

Methanol to Replace Sugar

Trygve Brautaset is an expert on metabolic engineering, the art of persuading bacteria to produce something that we want by 'tweaking' their genetic characteristics. Much of this knowledge has been developed in SINTEF/NTNU with financial support provided by the Research Council of Norway.

Dr Brautaset and his colleagues thought that it might be a good idea to use methanol instead of sugar as the raw material, since Norway has been blessed with ample supplies of natural gas, and methanol is a cheap alternative source of carbon on which bacteria grow rapidly. It has been a challenging task, but major breakthroughs arrived between 2001 and 2004.

The scientists cultivate a particular bacterial species and purify and cut up its mini-chromosomes. The sequence that they want is separated out and its genetic characteristics are modified. Electric discharges are used to reinsert the mini-chromosome into the bacteria, which can then be cultivated in large reactors to produce lysine.

Dr Brautaset was aware that American scientists had established theories and techniques for extracting and reinserting DNA into this particular bacterial species, and was curious to know whether their theories would hold up.

He travelled to Minnesota in 2001 where he worked in the University's laboratories. Chance led him to think out a new theory: could the genes that control a bacterium's ability to grow on methanol be located somewhere else than in their major chromosome? Might they be found in the mini-chromosomes, the 15 similar chromosomes that are about 200 times smaller than the main chromosome. Testing his idea, he found that it was correct: a gene with the ability to grow on methanol was located on the mini-chromosomes.

Published in 2004

Dr Brautaset took his mini-chromosomes back to Trondheim where, together with his colleague Øyvind Meidell Jakobsen, he identified five new bacterial genes that controlled growth on methanol. They also found two new genes on the main chromosome for growth on the same substrate.

Their work was published in the Journal of Bacteriology but full understanding of what their discovery could be used for did not emerge until the winter of 2004.

The fact that the 'methanol genes' were located on a mini-chromosome enabled the researchers to employ metabolic engineering techniques. The potential for improving the ability of bacteria to eat and metabolise methanol into lysine was greatly improved. The SINTEF scientists were no longer dependent on their US colleagues’ techniques, since they had developed their own tools and methods.

Three-Year Project

The result to date is that Trygve Brautaset has won international funding to continue this project, to which the Research Council of Norway has also contributed NOK3 million.

In the course of the next three years, the scientists expect to find out whether they can manipulate bacterial metabolism as they hope to do. The new bacteria, specially designed and built to use methanol as its source of energy, will be used in the project.

January 2010