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The Novo Nordisk Foundation has appointed Jens Nielsen, co-founder and chairman of the board of Biopetrolia, as the new head of the BioInnovation Institute (BII) from 1 February 2019. BII was established by Novo Nordisk Foundation to translate basic research into practical use to combat disease, improve health or conserve natural resources.
In an article published in the prestigious journal Cell, Biopetrolia-affiliated researchers were able to reprogram the yeast S. cerevisiae from traditional alcoholic fermentation to lipogenesis. In simpler terms, transform a yeast that was used for alcohol production into a yeast that produces fatty acids instead.
Through dozens of modifications to its metabolism, yeast cells rewired this way produce fatty acids because they need them to survive and grow. This strategy allowed 3production of more than 30g/L of free fatty acids, a significant improvement over previous attempts.
The use of 2A “self-cleaving” peptides can greatly simplify construction of complex pathways in yeast. However, not all 2A peptides are created equal. In an article published by researchers from Biopetrolia, Chalmers University and UNSEP, detailed characterization of multiple 2A peptide sequences to determine suitability for metabolic engineering applications in yeast was undertaken. The characterization pointed at particularly-efficient peptides, providing a new synthetic biology tool to allow rapid construction of metabolic pathways in yeast.
Biopetrolia has received a notice of allowance from the USPTO for a patent divisional application related to engineering hydrocarbon metabolism in yeast. The original patent, granted in 2017, claims yeast strains with modifications that allow increased production of hydrocarbons (used primarily as biofuels). The newly granted divisional patent claims yeast strains with modifications to allow for increased production of fatty acids, fatty alcohols and fatty aldehydes, which that can be used in a wide variety of industrial applications.
In an article published in PNAS, Biopetrolia-affiliated researchers generated a yeast platform strain with a simplified lipid metabolism. This strain allowed for a study of the fatty acid dynamics in lipid metabolism, which in turn enabled increased production of fatty acids through a redirected fatty acid metabolism pathway. The study provides new insights into the future development of lipid-related cell factories.
Biopetrolia has received an intention to grant of its Wax ester patent (EP2601292B1) from the EPO. The patent claims modifications to produce fatty acid ethyl esters (FAEEs) in fugal cells. FAEEs can be used in a variety of applications ranging from cosmetics to biofuels. The granting of this patent further solidifies Biopetrolia’s position in the microbial fatty acids space.
Biopetrolia-affiliated researchers at Chalmers reported on the engineering of yeast for production of fatty alcohols, recently published in the journal Metabolic Engineering. The production was increased through facilitating fatty alcohol secretion using heterologous transporters.
Secretion of fatty acid-derived products is an important stepping stone towards high level and robust production of these in yeast. By secreting the products, downstream purification and processing becomes simpler and more efficient. At the same time, as the product does not accumulate in the cell, cell fitness and overall production capacities could be significantly increased.
On last October, Jens Nielsen was awarded the prestigious ‘Eni Award’ by the Italian oil company Eni. Each year, Eni elects the best research projects related to energy efficiency, sustainability and environmental protection. This year, Jens Nielsen’s research on yeast metabolic engineering for the production of renewable fuels and chemicals was awarded the “Energy Frontiers” prize for exploration of new frontiers in energy technology. The technology has been recognized as “a significant contribution to the development of future energy solutions and a more sustainable society”.
On the same month, Prof. Nielsen also received the Gold Medal from the Royal Swedish Academy of Engineering Sciences. The medal was attributed for his innovative research in the field of systems biology and given in hand by Prince Carl Philip of Sweden.
In addition, Dr. Nielsen received the 2017 Eric and Sheila Samson Prime Minister’s Prize for Innovation in Alternative Fuels for Transportation. This prize is considered the world’s largest monetary prize awarded in the field of alternative fuels and it is given yearly to scientists who have made critical advancements in the field.
In a recent publication in the journal Metabolic Engineering, Biopetrolia-affiliated researchers at Chalmers reported on the engineering of yeast for production of medium chain aliphatic hydrocarbons. Medium chain hydrocarbons such as alkanes and alkenes are the main constituents of gasoline and jet fuels and are therefore attractive drop-in fuel for these purposes.
The process includes engineering of the yeast fatty acid synthesis machinery, so that the right fatty acid length is produced, followed by conversion of this fatty acid to an alkane or alkene form.
Biopetrolia is one of the industrial collaborators participating in Cell Nova, a center for development and production of next-generation biological drugs. The center has been approved for 40 MSEK funding from Vinnova in order to create next-generation cell factories for biopharmaceutical production as part of a broader effort to make Sweden a leading country in the development and production of biopharmaceuticals.
Chalmers and Biopetrolia researchers successfully engineered yeast cells for production of Docosanol with increased efficiency and selectivity, as reported by the paper in Nature Communications. Docosanol is a very long chain fatty alcohol mostly used as an emollient, emulsifier, and thickener in cosmetics. It is also commercialized as an FDA-approved antiviral agent for treatment of herpes simplex virus symptoms.
For producing docosanol, yeast cells were first engineered to produce very long chain fatty acids, which are present in only very low levels in the native cells. Subsequent engineering led to the conversion of said fatty acids into their fatty alcohol form in a very specific way free of contaminants from similar molecules.
Anastasia Krivoruchko was listed among 6 young researchers making names for themselves in the biotech industry by LABIOTECH.eu. This article features young (under 35) biotech researchers who are mostly active in entrepreneurship while still achieving surprising milestones in the academic environment.
Research by Biopetrolia and Chalmers researchers has recently been featured as the cover story in Natural Chemical Biology. The research involves modification of Fatty Acid Synthase, an enzyme that normally synthesizes long chain fatty acids. In this work the enzyme was re-engineered to produce short and medium fatty acids and methyl ketones, important compounds in the chemicals and fragrance industries. When combined with further manipulation of the yeast metabolism, a record level of short and medium chain fatty acids was achieved.
Biopetrolia is involved in an EU “Horizon 2020” project as part of an international consortium. Horizon 2020 is so far the biggest EU Research and Innovation programme ever and it aims to bring breakthroughs and innovative ideas from the lab to the market. The project CHASSY: “Model-Based Construction And Optimisation Of Versatile Chassis Yeast Strains For Production Of Valuable Lipid And Aromatic Compounds” aims to create robust yeast cell factories for different industrial products. The CHASSY consortium consists of several academic and industrial partners spread over a multitude of european countries.
A recent work by Biopetrolia-affiliated researchers was published in Biotechnology & Bioengineering. The publication describes engineering of yeast for the production of long-chain wax esters.
Long-chain wax esters are the main constituents of jojoba oil and are responsible for most of its properties. Furthermore, wax esters of different formulations are commonly used as cosmetic ingredients and biolubricants. The work is the first demonstration of the synthesis of very long-chain wax esters using yeast.
Biopetrolia has undergone a restructuring in its management, with Anastasia Krivoruchko taking the role of CEO and Florian David and Jens Nielsen the roles of COO and CSO, respectively. In addition, Henrik Dalbøge and Jan Svärd have joined as members of the Board of Directors. Henrik and Jan bring with them significant executive and business development experience in the biotech and specialty chemicals sectors.
Jens Nielsen, Florian David and Anastasia Krivoruchko have been interviewed by Chalmers about Biopetrolia. Chalmers and Biopetrolia share a symbiotic relationship where the research from SysBio (Systems and Synthetic Biology division from Chalmer’s Biology and Biological Engineering department) is converted into a reality brought to the public and applied in industry, allowing the growth of Biopetrolia as a sustainable and high-end solution. On the other hand, such a close relationship drives the institutional researchers at Chalmers into tackling solutions to real problems derived from society’s needs, increasing the impact and relevance of their research.
Biopetrolia – affiliated researchers have published a paper in Nature Communications on engineering yeast for high-level production of fatty acids and derived products. The engineered strains are so far the highest producer microorganism for fatty acids, reaching levels of up to 10.4 g/L. Using the same strategy, the authors were able to further engineer these cells to directly produce alkanes (molecular components of gasoline and diesel) and fatty alcohols valuable as formulation ingredients for personal care products.
The paper shows application of some of Biopetrolia’s patented principles on engineering yeast metabolism for efficient production of sustainable chemicals and brings the technology one step closer to a competitive leadership in industry.
Jens Nielsen was selected to receive the prestigious Novozymes Prize for his pioneering work on systems biology and metabolic engineering of microbial cell factories. The Prize is awarded in recognition of outstanding research or technology efforts that benefit the development of biotechnology and enables a total of 2.5 million DKK to be employed towards the development of promising new research projects.
“Receiving the Novozymes Prize is a really fantastic honour. I have always especially focused on understanding and modifying metabolism so that industry can apply this knowledge. Having unrestricted funds for riskier projects that can enable the new knowledge that is necessary to improve the technology is an enormous boost,” says Jens Nielsen.
Jens Nielsen explains further the applications of his research in this latest video by Novo Nordisk Foundation
Biopetrolia researchers have published a paper in ACS Synthetic Biology on the development and utilization of new yeast biosensor for simultaneously sensing and controlling yeast metabolism. The aim of this study was to demonstrate one case where yeast cells can use biosensors to control and improve production of a given chemical.
In this paper, the researchers engineered yeast cells to implement a genetic circuit capable of sensing one internal molecule and convert it into a precursor for plastic polymers. More specifically, the levels of the precursor metabolite malonyl-CoA are sensed in the cell by the genetic circuit, which activates production of enzymes that will then convert it to the final product 3-hydroxypropionic acid. The use of this system allows precise control of the metabolic pathway and increased production by 10-fold.
The paper displays some of the technology developed so far at Chalmers and Biopetrolia and exemplifies how it can be used in different combinations for varied applications.
In a recent publication, Chalmers and Biopetrolia-affiliated researchers demonstrate for the first time the production of gasoline and diesel constituents using the yeast Saccharomyces cerevisiae.
Until now, production of biofuels in yeast was limited to low energy molecules, such as ethanol. These are only compatible with modern transportation fuels in a low percentage. Higher energy molecules, such as alkanes (the main constituent of modern fuels such as diesel and gasoline) are therefore important to produce in a sustainable way. In this publication, researchers show it is possible to produce these same alkanes from sugar in a renewable way. This discovery opens up a possible reality where a renewable biofuel produced using yeast cells is totally compatible with modern transportation fuels.
The baker’s yeast (Saccharomyces cerevisiae) is today regarded as one of the most promising organisms to be used for the fermentation-based production of sustainable fuels and chemicals. In a recent review paper, Dr. Yongjin Zhou and colleagues explore the most recent scientific developments on the production of fatty acid-derived biofuels and chemicals in Saccharomyces cerevisiae.
Biopetrolia has recently been awarded a pre-Seed grant from Novo Seeds, an innovation investment interface from Novo, a company fully owned by the Novo Nordisk Foundation dedicated to investments on innovation, development and establishment on the biotech industry. The grant was awarded towards development of Biopetrolia’s fatty-acid overproducing platform strains and expansion of its scope towards production of value-added oleochemicals.
Biopetrolia was founded as of February 2014 as a patent-holding company from Jens Nielsen’s research group. This held intellectual property represents a rich portfolio of technology that has been generated by innovative research through many years on the field of metabolic engineering and synthetic biology of yeast cell factories.
Today, Biopetrolia proposes to create an evolving environment for the development of new yeast microbial factories that can bring real solutions to the industry of biofuels and fatty-acid derived chemicals.
Read the article by Innovations-kontor Väst [in Swedish]