Current Research | Funded Projects
funding (since 2007)
ABIONYS – Artificial Enzyme Modules as Tools in a Tailor-made Biosynthesis
June 2020 – May 2025 N° 865885
In order to tackle some of the prime societal challenges of this century, science has to urgently provide effective tools addressing the redesign of chemical value chains through the exploitation of novel, bio-based raw materials, and the discovery and implementation of more resource-efficient production platforms. Nature will inevitably play a pivotal role in the imminent transformation of industrial strategies, and the recent bioeconomy approaches can only be regarded as initial step towards a sustainable future. Operating at the interface between chemistry and life sciences, my ABIONYS will fundamentally challenge the widely held distinction separating chemical from biosynthesis, and will deliver the first proof-of-concept where abiotic reactions act as productive puzzle pieces in biosynthetic arrangements.
On the basis of our previous ground-breaking discoveries on artificial enzyme functions, I will create a significantly extended toolbox of biocatalysis modules by applying protein-based interpretations of synthetically crucial but non-natural reactions i.e. transformations that are in no way biosynthetically encoded in living organisms. My research will exploit these tools in multi-enzyme cascades for the preparation of complex organic target structures, not only to highlight the great synthetic potential of these approaches, but also to lay the groundwork for in vivo implementations. Eventually, the knowledge gathered from enzyme discovery and cascade design will enable to create an unprecedented class of bioproduction systems, where the genetic incorporation of artificial enzyme functions into recombinant microbial host organisms will yield tailor-made cellular factories.
Combining classical organic synthesis strategies with the power of modern biotechnology, ABIONYS is going to transform the way we synthesize complex and functional building blocks by allowing us to encode organic chemistry thinking into living production platforms.
ExtremoForm – Extremophile microorganisms as a source of highly productive enzymes for CO2 reduction to formic acid and other C1 fuels and platform chemicals
January 2020 – December 2023 No. 329512
with Prof. Silvan Scheller (A! Bio2) & Dr. Malin Bomberg (VTT Technical ResearchCentre, FI)
To achieve independence from fossil resources, a promising option for our society are the new bioapplications of formate or formic acid as hydrogen storage molecules and raw material for high-value chemicals. However, currently the chemical reduction of CO2 to formate requires expensive platinum group metals. The Aalto-VTT collaborational ExtremoForm project aims to mine new cold- and acidity-adapted enzymes from the environment. These biocatalysts with superior performance under extreme conditions will enable sustainable production of formic acid from CO2 at low temperatures. ExtremoForm will express, purify and engineer these enzymes to develop powerful sustainable biocatalytic tools for CO2 capture by exploiting Mo and W instead of the Pt group metals. The new ExtremoForm formate dehydrogenases will provide a great opportunity to expand the product scope to also other CO2-derived platform chemicals or solvents (e.g. formic esters, formamides).
SweetCu – Sugar-active Metalloenzymes as Novel Motifs in Synthetic Biocatalysis
September 2020 – August 2024 No. 331552
Academy project funding
Nature provides ingenious designs to perform chemical reactions in an elegant and efficient fashion by means of highly evolved enzyme catalysts. Those natural tools will inevitably play a crucial role in the imminent transformation of industrial strategies to value-added chemicals, as the implementation of more resource-efficient production platforms represents a key building block towards a more sustainable future. While being highly appealing, the more general application of enzyme catalysts in chemical synthesis is currently still hampered by the simple fact that many important transformations are not found in biosynthesis and as a result, biocatalysts for the particular reactions per se don't exist. The "reverse biomimetics" approach that is trying the unlock secondary, non-natural reactivities in biocatalysis constitutes a serious effort to revolutionize the field, and in recent years, we and others have successfully expanded the enzymes' reaction portfolio beyond biosynthesis.
The SweetCu proposal introduces another highly interesting protein platform that has great potential to further widen the reaction scope of natural catalysts. Here, a rather recently discovered class of sugar-degrading enzymes, the so-called lytic polysaccharide monooxygenases, serves as new biocatalytic scaffold. Thanks to an intriguing architecture featuring an exposed copper centre as redox-active reaction site, a reactivity profile similar to classical transition metal catalysts allows the metalloprotein to engage in abiotic transformations such carbene transfer processes, as recently revealed in preliminary studies by our group. SweetCu will elucidate the full capabilities of different reactivities including non-natural transferase-, isomerase. and mutase-type conversions. Additionally, mechanistic and protein engineering studies, as well as investigations of evolved variants of the enzyme on the depolymerization behaviours on non-sugar substrates, are going to supplement this in-depth assessment of an exciting new biocatalysis class.
Beyond Biosynthesis – Enzymes as Catalysts in Non-natural Synthetic Transformations
September 2016 – August 2020 No. 298250
The sustainable manufacture of chemical products through the development of novel and environmentally friendly processes will be a great challenge and an essential goal to be achieved in a post-fossil society. Biological systems with their natural catalysts – the enzymes – provide excellent properties in this regard, however, there still is a wide gap between the chemists' demands and Nature's offer. One major obstacle on the way to a truly bio-based machinery for the production of high-value chemicals is the lack of particular enzymes for a number of crucial chemical transformations. This Academy project aims for the in-depth examination of enzyme activities in important, non-natural reactions. Our results will provide both the tools and the understanding to bring the achievements of more than a century of successful chemical developments into a biological environment, and will serve as a foundation for the creation of novel tailor-made biosynthetic production lines.
CEVALOR – Cellular Factories for the Valorization of Biorefinery Chemicals
September 2019 – August 2022 No. 324854
Biological production platforms for the manufacture of chemical products pose a highly attractive solution en route to a bioeconomy-based society. Here, environmentally benign and resource-efficient conditions are characteristic features of microbial cellular factories and the tools of modern biotechnology permit the effective fine-tuning of these green reactors. Based on the recent development of novel enzymatic modules in the Aalto group of Synthetic Organic Chemistry, we envision the design and implementation of new biosynthetic pathways that will allow to address classical synthetic strategies for the valorization of biorefinery-derived furans. Exploiting the power of interdisciplinary approaches bridging classical chemistry with the life sciences, CEVALOR will enable the creation of sustainable, fermentative manufacturing strategies towards intermediates in the production of fragrances, pharmaceuticals, and bio-derived polymer precursors from non-fossil raw materials.