Group leader: Henrik Toft Simonsen
The main aim of the research group is to utilize the vast diversity of plant enzymes for production of valuable compounds, mainly mono- and sesquiterpenoids.
Utilizing a mix of photosynthetic cell systems, we want to show that plants offer unique opportunities for large-scale production of small natural products that are different for the current industrial applications.
We study heterologous expression of biosynthetic enzymes in photosynthetic cell factories. The current systems include the moss Physcomitrella patens to produce desired natural products or a precursor for chemical synthesis. We also utilize photosynthetic tissue culture systems in collaboration with Alkion Bioinnovations to produce drugs where the plant biosynthetic machinery is still unknown.
Benefits of Photosynthetic Cell Factories
Functional expression of terpene synthases (cyclases), cytochromes P450 and UGTs is one of the main limitations in metabolic engineering of terpenoid pathways in conventional microbial hosts. Membrane bound enzymes are especially difficult to express in microbial hosts. Here, developing a plant host platform that harbor all the in cellular machinery for the functional testing of biosynthesis related enzymes is the best way to overcome these problems.
The moss Physcomitrella patens
Moss is the ideal candidate for the production of natural products which are difficult of access. This simple plant grows efficiently in a cheap and simple media and can be maintained in large quantities in bioreactors.
Physcomitrella enables high efficient homologous recombination (Bach et al., 2014). This permits us to make specific and controlled recombination events and to generate transformants with predictable properties. Thus, stable production strain development neither requires crossing steps nor regeneration of whole plants.
The commercial aspects of these projects are developed in collaboration with Mosspiration Biotech IVS.
Mono- and Sesquiterpenoids
Mono- and Sesquiterpenoids allow plants to cope with various types of stress, and have often biological activities of high interest to human industries. Recent discoveries have led to an increased interest in the biological activity of the sesquiterpenoid class of metabolites, in particular in sesquiterpene lactones such as the anti-malaria drug artemisinin, and the anti-cancer drug thapsigargin (www.genspera.com). We have studied the biosynthesis of both molecules using different approaches. For Artemisinin we express the full biosynthesis in moss, whereas for thapsigargin we have to discover the biosynthesis first. We have published the initial steps of the biosynthesis (pickel et al, 2012) and this will be followed by further studies