WP4 – Synthetic Biology
WP4 is focusing on the transformation of simple carbon sources into high value products by microorganisms. This will be achieved by the design of efficient biosynthetic pathways in industrially relevant platform microorganism that allow the sustainable and economic production of complex molecules in order to reduce the number or even eliminate the necessity of synthesis steps by organic chemistry in production processes of small molecule drugs.
Specific activities of WP4 include:
- To make available new tool boxes to enable for efficient and time saving gene cloning procedures and assembly techniques to establish biosynthetic pathways. This will allow researchers to circumvent the hurdles of difficult transformations by concatenating genes of interest in one microorganism that are inherent to the complex microbial physiology.
- To provide novel technologies to access heterocycles and further molecules of interest for organic chemistry to be employed as functionalized building blocks
- To make use of either a single or multiple sustainable low-cost raw materials as starting material for the production of those small molecule targets
- To determine the limiting factors for the development of new synthetic pathways, the expression of individual enzyme components, location of component enzymes to different subcellular compartments, co-factor biosynthesis and regeneration, modeling of synthetic biochemical pathways in microorganisms and restrictions of available host systems (yeasts, bacteria).
- Legal, ethical and educational issues for new synthetic biology concepts jointly discussed with stakeholders and legal authorities.
- Evaluation of scalability, stability of the developed microbial production strains and conception of purification strategies for small molecules issued from synthetic biology.
Figure 1: An essential activity in WP4 is the development of a freedom-to-operate toolbox for a synthetic biologist.
N-heterocycles are prevalent in biologically active molecules and are increasingly attractive scaffolds in the development of new active pharmaceutical ingredients (API). In this context, the integration of enzymatic transformations holds particular potential forefficient and selective reaction sequences. We recently reported by database analysis the identification of three novel enantiocomplementary imine reductases that enable the enantioselective reduction of imines. The further combination of selective imine reductases with a flavin-containing amine oxidase in a novel one-pot reaction cascade highlights the potential of the multienzyme cascade for the efficient regio- and stereospecific synthesis of highly valuable N-heterocyclic building blocks.
P. N. Scheller, S. Fademrecht, S. Hofelzer, J. Pleiss, F. Leipold, N. J. Turner, B. M. Nestl, B. Hauer. Enzyme Toolbox: Novel Enantiocomplementary Imine Reductases, ChemBioChem 2014, 15(15), 2201-2204.