(One-carbon) metabolism
Methylotrophs and autotrophs are both capable of carbon fixation. Methylotrophs generate energy from reduced one-carbon compounds and are able to synthesize all of their cellular constituents from the one-carbon source. In contrast, autotrophs perform their biosynthesis from carbon dioxide and require a separate energy source. The most important reduced one-carbon substrates are methanol and methane, which offer industrial possibilities as renewable feedstocks.
The one-carbon metabolism of bacteria has intrigued our group and others for a long time, and elucidation of the mechanisms enabling growth solely on reduced one-carbon compounds has been a longstanding and challenging goal. Previously, we discovered the pathway and novel enzymes involved in the conversion of the central metabolic intermediate formaldehyde to carbon dioxide and demonstrated that tetrahydromethanopterin as well as methylofuran-dependent enzymes are involved in this process in a large variety of bacterial species. We are using carbon isotope-labeling strategies to uncover routes of one-carbon conversion in methylotrophs and conducted the first identification of the essential genome involved in the model methylotroph. Apart from elucidating the biochemistry of natural methylotrophs, the laboratory uses synthetic biology approaches and generated the first engineered methylotrophic Escherichia coli strain that requires methanol for growth.
The laboratory initiated research on half-lives of essential organic coenzymes in major model microorganisms. We developed long-term dynamic labeling experiments and found that PLP, NAD(P), flavins and coenzyme A are maximally long-lived, are propagated over generations of cells, and are essentially produced to compensate for dilution by growth. Currently, we are investigating coenzyme homeostasis under environmentally challenging conditions.
We operate high-resolution mass spectrometers for metabolomics of free-living and host-associated bacteria and develop novel software tools to facilitate LC-MS data analysis (eMZed, external pageDynaMetexternal page)
Keywords:
Metabolomics; Proteomics; Metabolic engineering; Carbon isotope labeling; Mass spectrometry; Pathway elucidation; Enzyme and coenzyme characterization; Synthetic Biology
Funding: