RWTH

Biodiesel production is usually accompanied by the production of 10% (w/v) glycerol as main low-value by-product, making it not yet economically competitive to petroleum-based processes. Recently, Ustilaginaceae fungi have attracted more attention due to their abilities of using crude glycerol to produce chemicals of industrial interest. Unlike established filamentous fungi, many Ustilaginaceae strains can grow in haploid and unicellular form, which are remarkably advantageous for industrial applications. Of note, U. trichophora was reported to have the highest titre for microbial malate production, even if the yield is still low. If the carbon lost during cultivation is suppressed, U. trichophora will be a novel candidate for industrial malate production and contribute directly to crude glycerol valorisation. However, the metabolic network and its function are not described for any Ustilaginaceae species. Isotope-assisted metabolomics approaches are powerful in exploring the metabolic network operation. By capturing the snapshot or the kinetics of metabolite pools, these approaches can guide metabolic engineering strategies to alter metabolic flux distribution and maximize target compound production. Therefore, this study aims to decipher the structure and dynamics of the metabolic networks of U. trichophora by using isotope-assisted metabolomics approaches. Results obtained in this research will guide ongoing efforts in metabolic engineering to maximize malate production from crude glycerol of U. trichophora. Further contributions will be made beyond the envisaged industrial applications, as the Ustilaginaceae are also investigated in the context of host-pathogen interactions and fundamental cell biology.

Over the past decades, metal catalysis has had a tremendous impact in chemistry, its adjacent disciplines and society overall, having gained an omnipresence in academic and industrial research worldwide. Numerous previously unthinkable transformations can nowadays be achieved in a selective and relatively mild manner owing to the metals' unique ability to trigger bond-making and breaking via pathways and principles that are inaccessible to metal-free processes. In this context, the global community has focused primarily on closed-shell, two electron processes for synthetic transformations. By comparison, the field of metalloradical catalysis has seen much less development, although metalloradicals are nature's preferred species to tame radical reactivities under non-precious metal-catalysis in numerous metalloenzymes. This is likely due to our currently limited understanding of metalloradical reactivity and its associated principles, and as such also limited ability to rationally design metalloradical catalysts and catalytic processes. A multidisciplinary approach, which capitalizes on the principles and insights of organic, organometallic and biological processes, will likely be key to meet the next frontier in this promising field. The objective of this proposal is to combine the tools of mechanistic, computational and synthetic organic/organometallic chemistry to explore catalysis with metalloradicals in synthesis, materials research and enzymatic processes. The proposed program will investigate some of the most pertinent questions in relation to the emerging area of remote functionalizations for the selective synthetic access to tailored molecules, olefin migrations and manipulations, and naturally occurring (enzymatic) metalloradical-catalyzed processes in the context of methane production and activation.