MegaSyn, a Hesse-wide research initiative, funded by the Hessen State Ministry of Higher Education, Research and the Arts, which focuses on the understanding of megasynthases in structure and function, and controlling megasynthases for directed product synthesis. The MegaSyn research program includes 12 groups from 5 different institutions.
The design of single proteins and complete biosynthetic pathways currently establishes as important tool in molecular life sciences. Driven by the increasing understanding in the structure and function of proteins and their complex interplay, possibilities arise to use natural systems (proteins, protein cascades, and microorganisms) for the directed and sustainable synthesis of biomolecules; thereby complementing traditional synthetic chemistry. Such approaches, aiming at developing “green” and “bioeconomic” synthetic methods, are of high sociopolitical importance. The research focus MegaSyn is concentrating on the biosynthetic production of technologically and pharmaceutically valuable compounds, as organic acids, antibiotics and immunosuppressives, which are synthesized by fatty acid synthases (FAS), polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). Megasynthases are gigantic multifunctional enzymes that covalently link small carbon- and amino acid units in an assembly like concept similarly as found in car manufacturing processes. Intermediates are bound to the megasynthase during synthesis until they are released in the final step as mature natural compound. MegaSyn is based on two synergistic developments, to which members of MegaSyn have substantially contributed during the last years; the newly established knowledge on the function and manipulation of FAS, PKS and NRPS megasynthases, and new and improved methods in structural biology, which were essential to pave the way for handling these complex proteins.