RESEARCH VISION & ONGOING PROJECTS
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 SvB Lab 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.
IV. From methanol to medicine – Sustainable microbial production of polyketide antibiotics
Polyketide antibiotics, such as erythromycin or tetracycline, are vital in treating infectious diseases. However, their current production by Streptomyces bacteria is often complex, expensive and unsustainable. Therefore, alternative production methods are urgently needed. In this project, an innovative concept for the sustainable microbial production of polyketide antibiotics from the inexpensive compound methanol will be realized by a metabolic engineering approach. Antibiotic-producing enzymes from Streptomyces will be transferred to Methylobacterium extorquens, a bacterium growing efficiently on methanol. Since these enzymes are complex molecular machines, their transfer into another microorganism is highly challenging. Successful antibiotic production from methanol will represent an important achievement and opens up a new research field.
