Larsson Lab

Our research activities are focused on developing the yeast Saccharomyces cerevisiae into an efficient producer (cell factory) of various chemicals and fuels by using a metabolic engineering approach. We have a long standing history of research in connection to optimization of bioethanol production. In more recent years we have also included butanol has an alternative biofuel that has many advantages compared to ethanol. S. cerevisiae is not a natural producer of butanol but by identification and insertion of suitable genes followed by protein engineering and careful selection of process conditions a novel efficient butanol forming organism/process will be developed. A similar approach has been used to transform S. cerevisiae into an ethylene producing organism. The aim of this project is to develop a sustainable process using renewable substrates for production of polyethylene that nowadays rely on finite fossil resources.
In order to be successful in our metabolic engineering projects we also focus on exploring the mechanisms for regulation/control of various metabolic pathways in the cell. Special attention has been directed towards the role of energy metabolism and the importance of adenine nucleotide levels but also redox metabolism is a field of interest.
The field of metabolic engineering in most cases relies on changing/adding the expression of proteins/genes in the host organism. To achieve proper expression and/or localization of the targetted protein it is necessary to understand the different layers of gene regulation involved. One project related to basic research into this area concerns the role(s) of, and regulatory mechanisms acting via the 3' untranslated region, using yeast as a model organism.

Current projects

Optimization of industrial ethanol production by development of process conditions to eliminate bacterial infections.
Contamination of lactic acid bacteria is a major problem in almost all industrial large-scale fermentations using yeast as a production organism. No matter whether it concerns fuel ethanol, potable alcohols, beer, wine, baker's yeast production or whether it is based on starch- or lignocellulose containing raw material it is inevitably a problem that somehow has to be dealt with. Even if many large-scale producers have managed to control and prevent bacterial infections to proceed out of hand it is still a leading cause of ethanol yield reductions and/or deterioration of product quality. In addition, more severe effects of lactic acid bacteria, such as slow down or premature arrest of the process even when the supply of sugar is plentiful, is frequently occurring. The aim of the project is to develop process/stress conditions such that multiplication of lactic acid bacteria is prohibited with a minimal effect on yeast activity.
Optimization of ethylene production by metabolic engineering of the yeast Saccharomyces cerevisiae.
Ethylene is one of the most used bulk chemicals in modern industry (e.g. in the plastics industry). However, since its production is based on the non-renewable supply of oil, it is desirable to find alternative production strategies. We have recently demonstrated that S. cerevisiae can be transformed into a producer of ethylene by the insertion of a bacterial ethylene forming enzyme (Pirkov et al, 2008). The main goal of this project is now to achieve higher yields of ethylene. This will be performed by e.g. metabolomic analysis coupled to predictive modelling followed by metabolic engineering of predicted target(s), by enzyme improvement and by optimization of growth parameters. 
Biobutanol production by metabolic engineering of Saccharomyces cerevisiae.
There is a strong interest in developing "green" alternatives to gasoline due to rising prices and climate change. Ethanol has traditionally had a strong position in this respect, due to the well established and comparatively cheap procedures for its production by yeast fermentations. But higher alcohols (such as butanol) would actually be more suitable as fuel, due to, e.g. their higher energy density and less corrosive properties. Traditionally, butanol is produced either chemically or from Clostridial fermentations (yielding 1-butanol). However, 1-butanol is highly toxic to most microorganisms, which limits the yields. We have therefore started a project to engineer yeast for production of 2-butanol from a glucose-based media, a process which is predicted to be redox neutral. The major tasks are (1) to improve tolerance to 2-butanol, (2) to identify and subsequently express the two genes encoding protein activities required for formation of 2-butanol, and (3) to optimize growth conditions and metabolism (the latter to be achieved by metabolic engineering of pathways predicted to be relevant).

Published: Thu 12 Feb 2015. Modified: Tue 09 Feb 2016