Major landmark in the 80 year history of Penicillin

Royal DSM N.V., the global Life Sciences and Materials Sciencescompany headquartered in the Netherlands, today announces that therenowned scientific journal "Nature Biotechnology" is publishing apaper in its October 2008 issue on a breakthrough analysis of the DNAsequence of the fungus Penicillium chrysogenum. The paper is theresult of a major research project initiated by DSM in which seveninternational research groups participated.

The unraveling of the DNA sequence of Penicillium chrysogenum is amajor landmark in the history of penicillin, arguably the mostimportant drug of the 20th century and discovered by Sir AlexanderFleming 80 years ago this month.

Gerard de Reuver, President of DSM Anti-Infectives, comments: "Theinsights gained through this research will help DSM Anti-Infectivesto improve current production methods for Beta-lactam antibiotics. Itwill also allow greater innovations in the development of productionmechanisms from which our customers and the patients in need of theseproducts will benefit too. We are committed to sustaining our worldleading position in these very important pharmaceutical products".

In order to gain a better understanding of the mechanisms by whichPenicillium chrysogenum produces antibiotics, and to improve theefficiency of this organism in the fermentation processes, DSMstarted a research project in 2004 to determine the complete DNAsequence of Penicillium chrysogenum and to elucidate of the functionsof the different genes. The project has resulted in a high-qualitygenome sequence of 32.2 million base pairs with 13,653 unique genes.The functions of around 6,000 of these genes could be predicted andthe first functional analysis of the genome has been reported.

Scientific breakthrough

"The unraveling of the DNA sequence enables us to study the highlycomplex physiology of Penicillium chrysogenum", explains Dr. Marcovan den Berg, principal scientist Metabolic Engineering and Screeningat DSM Anti-Infectives. "Never before has the sequence of this strainbeen mapped to this level or such important knowledge extracted. Itis an absolute leap forward in the field of these antibiotics and itwill generate many innovative development opportunities for bothclassical and new products. This project confirms DSM's leading rolein fungal biotechnology following last year's publication on anotherproduction workhorse of DSM, Aspergillus niger."

In February 2007 DSM published, also in Nature Biotechnology, a paperin which the company released the DNA sequence of the fungusAspergillus niger, a micro-organism that DSM uses for the productionof enzymes and other compounds that are mainly used in foodingredients. This research resulted in numerous patent filings by DSMand a whole range of new DSM products.

Follow-up research for the Penicllium chrysogenum project is nowbeing carried out by DSM in collaboration with academic partners in anumber of public-private partnerships in the Netherlands. Thisresearch has already resulted in several new patent filings by DSM.

DSM - the Life Sciences and Materials Sciences Company

Royal DSM N.V. creates innovative products and services in LifeSciences and Materials Sciences that contribute to the quality oflife. DSM's products and services are used globally in a wide rangeof markets and applications, supporting a healthier, more sustainableand more enjoyable way of life. End markets include human and animalnutrition and health, personal care, pharmaceuticals, automotive,coatings and paint, electrics and electronics, life protection andhousing. DSM has annual sales of almost EUR 8.8 billion and employssome 23,000 people worldwide. The company is headquartered in theNetherlands, with locations on five continents. DSM is listed onEuronext Amsterdam. More information: www.dsm.com

For more information:DSM Corporate Communications DSM Investor RelationsAndré van der Elsen Hans Vossentel. +31 (0) 45 tel. +31 (0) 45 57828645787162 fax +31 (0) 45 5782595fax +31 (0) 45 e-mail5740680 investor.relations@dsm.come-mail media.relations@dsm.com

Notes to editors and background information:

* Penicillium chrysogenum is a micro-organism that is used for the production of Beta-lactam antibiotics, such as penicillins and cephalosporins. These are converted into active pharmaceutical ingredients like amoxicillin, ampicillin, cephalexin and cefadroxil.

* The importance to humanity of penicillin should not be underestimated. Penicillin-derived antibiotics are still the world's most significant weapon against infectious diseases. This research has provided a landmark breakthrough in our understanding of Penicillium chrysogenum - the micro-organism that is used for the production of antibiotics - and this will be of benefit to all of humanity as it will help create purer products produced more sustainably and at a cheaper price, making these crucially important drugs more easily and widely available for all. This is important, because penicillin-derived antibiotics are likely to remain one of our most potent defenses against infectious diseases for several decades to come.

* The exact number of people using penicillin around the world every year is almost impossible to quantify but is more than a billion. Antibiotics account for about 8% of the world pharmaceuticals market.

* Last year's research into Aspergillus niger by DSM grew into one of the most important industrial genomics projects in Europe, and earned DSM a position among Europe's leading biotechnology companies. DSM products that were developed as a result of this research include: PeptoPro® (ingredient for muscular recovery after physical exertion); Brewers ClarexTM (enzyme for preventing chill-haze in beers); and PreventASeTM (enzyme for preventing the formation of the toxic compound acrylamide during baking or frying of certain foodstuffs).

Partners

DSM scientists carried out the research on the Penicilliumchrysogenum genome in collaboration with research partners in theNetherlands, Germany, Spain and the USA.

Delft University of Technology, Professor Jack Pronk, head of theIndustrial Microbiology department: "This genome sequence will helpus to identify the many mutations that, over the course of half acentury of intensive strain improvement, have transformed naturallyoccurring Penicillium chrysogenum, which produces only negligibleamounts of penicillin, into a highly efficient antibiotics producer.Insight into the mechanisms and dynamics of genome change in thisunique model system will be invaluable for the rational design ofother strain improvement programs."

Groningen University. Professor Arnold Driessen, head of theMolecular Microbiology -department: "With the aid of the genomesequence we will now be able to elucidate the last unresolvedmechanistic questions in antibiotics biosynthesis that have proven tobe difficult to tackle otherwise. This for instance concerns theelusive transport of penicillins and cephalosporins out of the cell.These insights will be instrumental for the future synthetic biologybased development of novel production processes."

Title of the paper published in Nature Biotechnology

"Genome sequencing and analysis of the filamentous fungus Penicilliumchrysogenum" :http://www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.1498.html

Press release-pdf: http://hugin.info/130663/R/1255097/273505.pdf

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