Research

MossTech is all about mosses – taking these lovely plants from the shadows of the forest the spotlight of green biotechnology.

Mosses
The moss lineage diverged from vascular plants about 450 million years ago and has maintained a small and rather simple vegetative body structure with few specialized cell types. Unlike vascular plants, the haploid gametophyte dominates the life cycle, while the diploid sporophyte is short-lived and completely dependent on the gametophyte. Physcomitrella patens (our favorite species) has been used as a model for studies on plant evolution, development and physiology for more than 40 years, including a full genome sequence. P. patens is already used in biotechnology for the safe production of complex biopharmaceuticals and for fragrance production. One example is the production of the highly glycosylated peptide hormone erythropoietin (EPO). Production of EPO was carried out in a P. patens Delta-fuc-t Delta-xyl-t strain, deficient in the enzymes responsible for the plant-specific core-bound alpha 1,3-fucose and beta 1,2-xylose. Thus, the final product will have a more humanized glycosylation pattern and therefore be non-immunogenic.

Moss biotechnology
P. patens has a number of features that make it an attractive production system. It can be grown in sterile liquid cultures. It grows photoautotrophically in a simple inorganic media without the need for phytohormones, vitamins or a carbon source. It can be grown in large continuous P. patens cultures where it is maintained as protonema (the haploid phase), this ensures a stable genetic background in the continuous bioreactor cultures.

Lately, novel transformation technologies like in-vivo assembly of DNA and CRISP-Cas9 has been applied to P. patens. Even though it already performs homologues, recombination very efficiently the novel technologies make this even better.

Moss Chemistry
Mosses are characterized by a low degree of structural complexity, which is compensated by a high degree of chemical complexity, including both unique substances and more generally distributed metabolites. Several moss species are known to produce small molecules that resemble commercial fine chemicals. Thus, describing how to utilize this biodiversity will open a new avenue of unique production platforms with different production capacities. Recent studies by MossTech participants have highlighted the use of mosses to produce highly valuable compounds such as terpenoids.

Challenges
Green cell factories are great biosynthetic platforms for the production of both fine and bulk chemicals of all kinds from the smallest molecule to the largest protein. MossTech will study and understand the challenges in mosses, such as gene regulation, protein expression, biosynthesis of products, and formation of storage compartments that can be utilized for industrial production. Likewise, a broad overview of the biodiversity of hosts will provide new and better hosts to the biotech industry.

Main research objectives
The 6 PhD projects (please see individual links) in MossTech will address the challenges described. Overall MossTech will develop novel biotechnological tools and establish at least 10 specialized moss species as new biotechnological platforms for fine chemical and protein production. MossTech will also provide new moss mutants optimized for production to be used directly in industrial applications.

With the applied approach, MossTech will also address the fundamental understanding of moss bioengineering, terpenoid biosynthesis regulation, protein expression and evolution of specialized metabolites in mosses. This will significantly contribute to a better understanding of basic plant biology and biochemistry, along with our applied goals.

 

Contact

Henrik Toft Simonsen
Associate Professor
DTU Bioengineering
http://www.mosstech.eu/Research
20 NOVEMBER 2018