Development of a modular platform for the efficient, biobased and tailor-made synthesis of lignans
Objective
Lignans are natural compounds derived from the shikimic acid biosynthetic pathway. Many lignan containing plants (like Podophyllum) have been used for centuries as sources for agents to treat human disorders. Lignans can be used as both pharmaceutical as leading compounds for novel drugs, and nutraceutical as ingredients of healthy diets to reduce the risks of lifestyle-related diseases. Seasonal fluctuation and low titers of target lignans in plants, of which some are critically endangered species, are a major drawback for their cost-efficient and stable supply. Thus, the development of new routes for an efficient and sustainable lignan production is of high interest. LignaSyn aims at establishing novel recombinant multi-enzyme cascades in industrially preferred and generally recognized as safe microbial strains for stable, efficient and sustainable lignan production starting from renewable resources like sugar or molasses.
The partners within the LignaSyn consortium will focus on the establishment and optimization of enzymatic modules to generate a biobased lignan synthesis platform: ”Precursor modules” will be developed for de novo synthesis of cinnamyl alcohol derivatives (monolignols) (RWTH supported by Phytowelt). The monolignols will undergo dimerization within “key modules”, followed by ring-modification steps within “designer modules” to give prototype lignans like sesamin and matairesinol (HHU, supported by Phytowelt). Individual synthetic modules and the entire E. coli-based platform will be optimized regarding productivity and stability using metabolic analysis (TUD, supported by HHU, RWTH and Phytowelt). Lignan production and down-stream-processing (DSP) at lab scale will be optimized by Phytowelt and TUD.
Funding
Project partners
- Prof. Vlada B. Urlacher (coordinator) – Heinrich-Heine-University Düsseldorf – Germany
- Dr. Ulrich Commandeur, RWTH Aachen University, Institute for Molecular Biotechnology, Aachen – Germany
- Prof. Dr. Stephan Lütz, Technische Universität Dortmund, Bio- und Chemieingenieurwesen, Bioprozesstechnik, Dortmund – Germany
- Dr. Guido Jach, Phytowelt GreenTechnologies GmbH, Phytowelt R&D-Facilities, Köln –Germany