Bioengineering of terpenoids – TerpFactory

The goal of TerpFactory is to implement a collaborative research and development platform between the Institute of Plant Molecular Biology of CNRS in Strasbourg (IBMP) and the company dedicated to the production of plant-derived bioactive natural compounds, Plant Advanced Technologies (PAT). Plants constitute the main source of bioactive compounds for the pharmaceutical and cosmetic industries. Aroma and scent industry is also in strong demand of « natural » ingredients. A large number of such ingredients have a high cost and are produced from plants sources available in limited amounts or at risk of extinction. TerpFactory has for objective to generate biotechnological tools allowing the production of such ingredients with process development and marketing carried-out by PAT.

High added value target compounds will be selected in common agreement between the company and the laboratory, based on potential market(s) and project feasibility. The company will define the optimal plant source (plant species, cultivar, source organ) taking into account the target molecule content. The task of IBMP will be to identify the metabolic sequences leading to the selected compounds, to isolate the genes encoding the enzymes involved in their biosynthetic pathway via a RNAseq approach targeted on the source plant and organ defined by PAT. Based on the predicted pathway, IBMP will select the candidate genes and the corresponding enzymes will be expressed in microorganisms (usually yeast) or, if required, in a model plant transient expression system (Nicotiana benthamiana). After functional characterization of the enzymes, reconstruction of the metabolic pathways will be carried via multigene transient expression in planta for validation. PAT will provide the metabolic precursors required as analytic references and for enzyme assays, thanks to preliminary plant extractions or from his organic synthesis laboratory. Upon common agreement, IBMP may proceed the optimisation of the enzyme expression (recoding, mutagenesis) and to a reconstruction of validated pathway in yeast. All tools will be transferred to PAT for transformation of the PAT platform plant (Ipomea batatas) and for optimisation of the production process.

In parallel to this targeted strategy, a synthetic biology approach will be considered for enzymatic functionalisation of bioactive compounds of interest for PAT. The conversion (mainly hydroxylation) of molecules provided by PAT will be tested with enzymes of the collection of the IBMP and resulting metabolites evaluated for antioxidant, anti-inflammatory and anti-melaninogenic activities by PAT. Another synthetic biology approach will consist in a combinatorial assembly of the enzymes generated form plants targets of the present project with enzymes already available at the IBMP to generate new structures that will be tested for activity by PAT.