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Predictive and Accelerated Metabolic Engineering Network

Periodic Reporting for period 1 - PAcMEN (Predictive and Accelerated Metabolic Engineering Network)

Reporting period: 2016-10-01 to 2018-09-30

The United Nations have adopted a historical agreement on reduction of carbon dioxide emissions on the 12th of December 2015. The ambition is to hold the increase in the global average temperature to well below 2°C above the pre-industrial level, which means limiting the CO2 emissions to 40 gigatonnes per year in 2030. This will require to double utilization of biomass and waste. A shift towards bio-based production of chemicals and fuels can significantly reduce our dependency on oil and gas and lead to a more environmentally friendly economic growth. The main challenge for industrial biotechnology is the development of novel cell factories that can efficiently convert feedstocks into the product of interest at minimum processing cost. Currently, it takes over 50 man-years and over $50 million to develop a cell factory, an investment that is difficult to finance and recover. Hence, there is a critical need for novel technologies and approaches that can change the paradigm and deliver novel cell factories faster and cheaper. For that we need researchers with interdisciplinary scientific training and with insight into the industrial biotechnology processes and business.
The European Training Network on Predictive and Accelerated Metabolic Engineering Network (PAcMEN) is training sixteen Early Stage Researchers (ESRs) in the following complementary research disciplines, which together offer an opportunity to revolutionize the development of cell factories for biotechnology:
• Systems Biology and Modeling,
• Synthetic Biology and Protein Engineering, and
• Applications for Development of New Biorefinery Processes.

The overall objective of PAcMEN research programme is to bring step-change innovation into development of cell factories for industrial biotechnology, where modeling and utilization of ‘omic data will enable more predictive cell factory design and synthetic biology will accelerate strain construction and screening. The ultimate research aim is to cut down the cost and time of developing new cell factories.
"The research covers three disciplines: metabolic modeling, synthetic biology, and metabolic engineering. The main achievements can be summarized as following.
Metabolic Modeling: the genome-scale model of yeast Saccharomyces cerevisiae was extended with thermostability and regulatory constraints. A thermodynamic model of oleaginous yeast Yarrowia lipolytica is under construction.
Synthesis Biology: The ESRs have uncovered the effect of translation initiation sequence on protein expression, designed new biosensors, and improved the technology for enzyme engineering and screening.
Metabolic Engineering: The ESRs have engineed novel yeast strains that can convert sugar into value-added products as fatty alcohols, lactones, and aromatics. They have also created strains that are independent on complex nutrients supplementation.
Dissemination: Six peer-reviewed publications have already been published by PAcMEN ESRs and many more publications are currently in preparation. The updated list of publications can be found on the PAcMEN official website www.pacmen-itn.eu. All PAcMEN papers are published with open access. The results have also been presented at over 14 international conferences, e.g. Metabolic Engienering 12, 33rd International Specialised Symposium on Yeast (ISSY33), Enzyme Engineering XXIV, and others. Moreover the project results have been dissiminated to general public through different events and media: Open Science Night, research exhibitions for students, ""skype a scientist"", and other.
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In the second half of the project, PAcMEN will further advance the research on genome-scale modeling, enzyme engineering, and yeast cell factories engineering. The results will be exploited in collaborations with industrial partners and disseminated to scientific community and general public.
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