Research in the lab of Lennart Schada von Borzyskowski focuses on understanding and engineering the versatile metabolism of bacteria. Lab members strive to gain fundamental knowledge by investigating the physiology of environmental microbes and apply these discoveries to develop sustainable solutions for the benefit of society. Techniques from diverse fields such as biochemistry, structural biology, metabolic engineering, and microbial ecology are combined to characterize previously unknown enzymes and metabolic pathways, and subsequently implement them in diverse host organisms to generate novel biological functions that help to tackle global environmental challenges.

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Research

Bacteria are everywhere. They can make a living in the deep sea, in hot springs, in the human gut, or in heavily polluted environments. This is made possible by their astounding metabolic versatility, their ability to obtain nutrients under diverse conditions in an ever-changing environment. This ability is mediated by a large array of enzymes and metabolic pathways. Research in the lab of Lennart Schada von Borzyskowski focuses on the discovery and characterization of novel biocatalysts and on the engineering of heterologous metabolic pathways in various host microorganisms. To this end, an interdisciplinary combination of methods is applied, including enzyme assays based on photometry or mass spectrometry, protein crystallography, high-throughput genetic screens, omics techniques, and directed evolution.

The group of Lennart Schada von Borzyskowski is currently pursuing research on the following topics:

I. Identification and characterization of novel enzymes and pathways by deciphering the metabolic regulation of uncultured bacteria
Numerous metabolic pathways of microbes remain undiscovered so far, decreasing our ability to understand how bacteria interact with their environment. This is due to the lack of appropriate tools for forward and reverse genetics to find new enzymes and pathways in non-model microorganisms. We are developing and utilizing high-throughput approaches that allow targeted screening of genetic libraries for previously undiscovered enzymatic activities, and subsequently characterize and apply the newly discovered biocatalysts.

II. Experimental simulation of horizontal gene transfer in marine microbiomes by metabolic engineering
There are two central requirements for all living cells: the assimilation of carbon to generate biomass, and the conservation of energy to enable growth and reproduction. For both purposes, a broad variety of metabolic modules exists. However, preliminary data point towards the fact that specific metabolic modules are phylogenetically scattered. Furthermore, it is well known that metabolic modules can be transmitted by horizontal gene transfer. This poses the questions (I) why not all bacteria that live in similar habitats possess these metabolic modules and (II) how the fitness of a bacterium changes when it receives a novel metabolic module via horizontal gene transfer. We address these questions using experimental approaches that unite bacterial physiology and its evolution with metabolic engineering.

III. Synthetic biology-guided development of marine Proteobacteria towards applications in bioremediation and blue biotechnology
In the past two decades, the disciplines of synthetic biology and metabolic engineering have taken large steps forward, but have mainly utilized model organisms such as Escherichia coli or Saccharomyces cerevisiae. These microorganisms are unsuited for marine habitats, hampering our ability to use synthetic biology to address pressing ecological challenges. We address this issue by developing genetically tailored strains of marine bacteria that can be used for bioremediation and blue biotechnology and apply them to the degradation of microplastics or petrochemicals as well as the sustainable production of value-added compounds.

Biography

Lennart Schada von Borzyskowski obtained an undergraduate degree in Applied Natural Science in Freiberg (Germany), followed by a 12-month research visit to the California Institute of Technology (Pasadena, USA), where he elucidated the structure of a protein complex involved in carcinogenesis. Between 2012 and 2016, he obtained his PhD in the fields of biochemistry and metabolic engineering at ETH Zürich (Switzerland) in the laboratories of Tobias Erb and Julia Vorholt. His doctoral work focused on the design and realization of synthetic metabolic pathways and engineered bacteria to capture the greenhouse gas carbon dioxide. Thereafter, Dr. Schada von Borzyskowski performed postdoctoral research at the Max Planck Institute for Terrestrial Microbiology in Marburg (Germany) from 2016 to 2021. During this period, he characterized the b-hydroxyaspartate cycle (BHAC), a metabolic pathway that mediates trophic interactions between algae and bacteria in the global oceans. Subsequently, he applied the enzymes of the BHAC to improve the metabolism of bacteria and plants, which will lead to applications in biotechnological plastic degradation and the generation of crops with increased yield.

Currently, Dr. Lennart Schada von Borzyskowski is an Assistant Professor in the Microbial Sciences Cluster at the Institute of Biology Leiden (IBL). His research continues to combine the investigation of natural bacterial metabolism and the biological engineering of synthetic metabolism in order to understand the diversity of microbial biochemistry and apply it towards sustainable biotechnological approaches.

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