Jens Nielsen | AIChE

Jens Nielsen

BioInnovation Institute

Prof. Jens Nielsen is a world-leader in systems biology of metabolism and he has used his competence to engineering yeast for production of fuels, bulk chemicals, speciality chemicals, nutraceuticals, food and feed ingredients, and pharmaceuticals, for studying function of the human gut microbiota, and for identification of cancer biomarkers. In all three areas he has demonstrated the ability to translate his cutting edge science into use for the society in the form of consultancies, foundation of spin-out companies and filing of patent applications that have been licensed to international biotech companies.

Prof. Nielsen has so far published more than 700 papers in international scientific peer-reviewed journals, with more than 72,000 citations (current H-index 124). Prof. Nielsen has received numerous international awards and honours for his research, including the Gold Medal from the Royal Swedish Academy of Engineering Sciences, the ENI Award (Italy), the Prime Ministers Prize for Innovation in Alternative Fuels for Transportation (Israel), the Novozymes Prize (Denmark), Nature Mentors Award (UK), Merck Award for Metabolic Engineering (USA), and Amgen Award for Biochemical Engineering (USA). He has been elected to the National Academy of Engineering (USA), the National Academy of Science (USA), the Chinese Academy of Engineering, the Swedish Royal Academy of Science (KVA), Swedish Royal Academy of Engineering (IVA), the Royal Danish Academy of Science and Letters and the Danish Academy of Technical Sciences.

Much of his research has been translated to industry either through licensing of inventions to multi-national companies or through forming the basis for six biotech companies he has founded. Prof. Nielsen is also an active contributor to the scientific community through acting as editor of six key journals and membership of the editorial board of another 20+ journals, and through taking leadership in the community; he is founding president of the International Metabolic Engineering Society (IMES).

The core of Prof. Nielsen’s scientific contributions are: 1) creation of in silico systems biology and metabolic engineering tools for analyses and design of metabolism; 2) in vivo engineering of microorganisms and their metabolism for biological production of valuable chemicals and biological molecules; 3) analysis of functional interactions between individual species in complex microbial ecosystems such as the human gut microbiome; and 4) analysis of metabolic alterations in human cells in connection with disease development and progression, and use of this for identification of novel biomarkers and drug targets.

Using these technologies Prof. Nielsen has engineered yeast to produce more than 20 different chemicals that are all of industrial interest and found applications in many different commercial or industrial segments. Among these are: 1) resveratrol, an anti-oxidant used as dietary supplement and a cosmetic ingredient; 2) 3-hydroxypropionic acid (3HP) that is used to make acrylates, a group of super-absorbing polymers used in hygiene products; 3) santalene, a sesquiterpenoid used as a perfume ingredient, and used to replace sandal-wood oil which is scarce; 4) farnesene, a sesquiterpenoid used as a blend-in diesel fuel; 5) both long and short chain length alkanes that can be used as diesel and jet fuels; 6) pharmaceutical proteins such as insulin analogs; 7) polyketides that can be used as potential new pharmaceuticals and antibiotics; 8) coumaric acid that can used as chemical building block for production of solvents, polymers and dies; 9) haemoglobin that can be used a blood substitute; and 10) ornithine that can be used as a dietary supplement and as a precursor for production of pharmaceutical or nutraceutical polyamines, such as spermidine.

Besides this wide variety of yeast based processes for biological production, Prof. Nielsen has worked on improving enzyme production by other microorganisms, such as bacteria (Bacillus) and filamentous fungi, production of organic acids by filamentous fungi, production of antibiotics by Actinomycetes and filamentous fungi, and for improvement of the classical ethanol production process for the bioethanol industry. Based on this more than 40 patent applications have been filed (many have issued), of which most have been translated for use in industry. Several of these patents were the basis for establishment of new companies, e.g. 1) Fluxome that developed a novel process for production of the dietary supplement resveratrol, a process that was acquired and continued by the Swiss company Evolva who is now a main producer of this compound; 2) MycoTeQ that screened filamentous fungi for identification of novel antibiotics; 3) Biopetrolia, a company that is developing novel bioprocesses for production of speciality chemicals; 4) Chrysea, a synthetic biology company that aims to produce novel anti-ageing compounds. One of the classical bioprocess is production of ethanol, using yeast as a cell factory, to be used as biofuel. Prof Nielsen’s discoveries on increased ethanol yield and reduced glycerol were patented, licensed and translated to industry.

Additionally, industrial bioethanol production would benefit from operating at higher temperatures due to a reduction in cooling costs of large bioreactors and increase the efficiency of expensive enzymes for biomass pre-treatment. However, yeast does not survive well above 30°C. With this in mind, using adaptive laboratory evolution and systems biology Prof Nielsen and his team discovered a new molecular mechanism that renders yeast thermotolerant (Science (2014) 346:75-78). The findings have large industrial potential, for first- and for second-generation bioethanol production from biomass, and is currently being evaluated for industrial implementation. Among other key biological production processes Prof. Nielsen has been involved can be mentioned: 1) Early engagement in setting up a completely novel production process for the antibiotics cephalexin at the Dutch company DSM, which involved establishment of a novel microbial based production of adopoyl-7-ADCA by a filamentous fungus; and 2) Identification of the metabolic pathway associated with production of oxalic acid by the filamentous fungus Aspergillus niger, that is used for production of industrial enzymes, and use of this information to eliminate production of this organic acid.

Another use of Prof. Nielsen’s competences on systems biology of metabolism have been for studying metabolic interactions between individual bacteria in complex ecds osystems such as the human gut or yoghurts containing multiple probiotics such as Activia. Thus, Prof. Nielsen has through collaboration with the French company Danone gained insight into how five individual bacteria used to produce Activia interacts and ensures survival of key species when they enter the human gastrointestinal tract. Furthermore, his work on modelling the metabolism of gut symbionts has been used to gain insight into how amino acids used in feed to piglets ensures establishment of a more stable gut microbiome in pigs, and hereby enables faster growth of piglets. This has enabled the Japanese company Ajinomoto to design improved feeds for pigs. His bioinformatics analysis of metagenome data obtained from human fecal samples has also been used to identified new prospective probiotics that can be used to improve the health status of subjects with elevated risks of developing metabolic diseases such as type-2-diabetes. This work has formed the basis for establishment of the spin-out company Metabogen AB that focus development of next generation probiotics and was sold to Biogaia AB in 2018.

Finally, Prof. Nielsen has used his knowledge on metabolism to study how human metabolism is altered in connection with a range of different diseases such as type-2-diabetes, obesity, non-alcoholic liver disease and cancer. Based on systems biology analysis has been able to identify metabolic re-programming associated with different human diseases. Specifically this allowed him to identify novel signature pathways associated with different kinds of cancers, and further use this for development of a so-called systems biomarker where a panel of 19 metabolites are measured and used to generate a biomarker score that has very strong predictive strength for presence of a tumors. Work in this area has progressed most on development of a cancer biomarker for clear cell renal carcinoma, where the biomarker has been validated in several different clinical trials and is now being evaluated for use in the clinic for evaluation of recurrence following tumor removal. There has been filed several patent applications based on this work and these patents have been transferred to the spin-out company Elypta AB that is currently commercializing this technology.