A5044028530- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Protein Structure and Dynamics
- Microbial Fuel Cells and Bioremediation
- Biochemical Acid Research Studies
- Biofuel production and bioconversion
- Gene Regulatory Network Analysis
- CO2 Reduction Techniques and Catalysts
- Bacterial Genetics and Biotechnology
- Amino Acid Enzymes and Metabolism
- Algal biology and biofuel production
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Microbial metabolism and enzyme function
- Origins and Evolution of Life
- Fungal and yeast genetics research
- Microbial Community Ecology and Physiology
- Viral Infectious Diseases and Gene Expression in Insects
- Gene expression and cancer classification
- Metalloenzymes and iron-sulfur proteins
- Genomics and Phylogenetic Studies
- Process Optimization and Integration
- Carbon dioxide utilization in catalysis
Max Planck Institute of Molecular Plant Physiology
2016-2025
Weizmann Institute of Science
2004-2019
Max Planck Society
2015
Charité - Universitätsmedizin Berlin
2013
Hebrew University of Jerusalem
2013
Genes are often characterized dichotomously as either housekeeping or single-tissue specific. We conjectured that crucial functional information resides in genes with midrange profiles of expression.To obtain such novel genome-wide, we have determined the mRNA expression levels for one largest hitherto analyzed set 62 839 probesets 12 representative normal human tissues. Indeed, when using a newly defined graded tissue specificity index tau, valued between 0 and 1 tissue-specific genes,...
The kinetic parameters of enzymes are key to understanding the rate and specificity most biological processes. Although specific trends frequently studied for individual enzymes, global rarely addressed. We performed an analysis k(cat) K(M) values several thousand collected from literature. found that "average enzyme" exhibits a ~0 s(-1) k(cat)/K(M) ~10(5) M(-1), much below diffusion limit characteristic textbook portrayal kinetically superior enzymes. Why do exhibit moderate catalytic...
The laws of thermodynamics constrain the action biochemical systems. However, thermodynamic data on compounds can be difficult to find and is cumbersome perform calculations with manually. Even simple questions like ‘how much Gibbs energy released by ATP hydrolysis at pH 5?’ are complicated excessively search for accurate data. To address this problem, eQuilibrator couples a comprehensive database properties reactions powerful online calculation interface. web interface...
Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains life, not sugar-consuming organisms use canonical Embden–Meyerhoff–Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative pathways, most common which Entner–Doudoroff (ED) The prevalence ED puzzling it produces only one ATP per glucose—half much EMP We argue that diversity prokaryotic may reflect tradeoff between pathway’s energy...
Carbon fixation is the process by which CO 2 incorporated into organic compounds. In modern agriculture in water, light, and nutrients can be abundant, carbon could become a significant growth-limiting factor. Hence, increasing rate of major importance road toward sustainability food energy production. There have been recent attempts to improve specificity Rubisco, carboxylating enzyme operating Calvin–Benson cycle; however, they achieved only limited success. Nature employs several...
The living world is largely divided into autotrophs that convert CO2 biomass and heterotrophs consume organic compounds. In spite of widespread interest in renewable energy storage more sustainable food production, the engineering industrially relevant heterotrophic model organisms to use as their sole carbon source has so far remained an outstanding challenge. Here, we report achievement this transformation on laboratory timescales. We constructed evolved Escherichia coli produce all its...
We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence FLS enables design new carbon fixation pathway, consisting small number thermodynamically favorable chemical transformations that convert formate sugar in central metabolism. pathway is predicted to use more efficiently and with less backward flux than any naturally occurring assimilation...
Can a heterotrophic organism be evolved to synthesize biomass from CO2 directly? So far, non-native carbon fixation in which precursors are synthesized solely has remained an elusive grand challenge. Here, we demonstrate how combination of rational metabolic rewiring, recombinant expression, and laboratory evolution led the biosynthesis sugars other major constituents by fully functional Calvin-Benson-Bassham (CBB) cycle E. coli. In bacteria, is performed via CBB cycle, while reducing power...
In metabolism research, thermodynamics is usually used to determine the directionality of a reaction or feasibility pathway. However, relationship between thermodynamic potentials and fluxes not limited questions directionality: also affects kinetics reactions through flux-force relationship, which states that logarithm ratio forward reverse directly proportional change in Gibbs energy due (ΔrG'). Accordingly, if an enzyme catalyzes with ΔrG' -5.7 kJ/mol then flux will be roughly ten times...
Turnover numbers, also known as kcat values, are fundamental properties of enzymes. However, data scarce and measured in vitro, thus may not faithfully represent the vivo situation. A basic question that awaits elucidation is: how representative values for maximal catalytic rates enzymes vivo? Here, we harness omics to calculate kmax(vivo), observed rate an enzyme inside cells. Comparison with from Escherichia coli, yields a correlation ofr(2)= 0.62 log scale (p < 10(-10)), root mean square...
Abstract Six CO 2 fixation pathways are known to operate in photoautotrophic and chemoautotrophic microorganisms. Here, we describe chemolithoautotrophic growth of the sulphate-reducing bacterium Desulfovibrio desulfuricans (strain G11) with hydrogen sulphate as energy substrates. Genomic, transcriptomic, proteomic metabolomic analyses reveal that D. assimilates via reductive glycine pathway, a seventh pathway. In this is first reduced formate, which condensed second generate glycine....
Bacterial growth depends crucially on metabolic fluxes, which are limited by the cell's capacity to maintain enzymes. The necessary enzyme amount per unit flux is a major determinant of strategies both in evolution and bioengineering. It parameters (such as kcat KM constants), but also metabolite concentrations. Moreover, similar amounts different enzymes might incur costs for cell, depending enzyme-specific properties such protein size half-life. Here, we developed cost minimization (ECM),...
Abstract The capture of CO 2 by carboxylases is key to sustainable biocatalysis and a carbon-neutral bio-economy, yet currently limited few naturally existing enzymes. Here, we developed glycolyl-CoA carboxylase (GCC), new-to-nature enzyme, combining rational design, high-throughput microfluidics microplate screens. During this process, GCC’s catalytic efficiency improved three orders magnitude match the properties natural -fixing We verified our active-site redesign with an...
Significance The cultivation of microbial biomass, which is rich in proteins as well other nutrients, can play a vital role achieving food security while mitigating the negative environmental footprint agriculture. Here, we analyze efficiency associated with using solar energy for converting atmospheric CO 2 derived from direct air capture into biomass that feed humans and animals. We show production foods outperforms agricultural staple crops terms caloric protein yields per land area at...
Protein levels are a dominant factor shaping natural and synthetic biological systems. Although proper functioning of metabolic pathways relies on precise control enzyme levels, the experimental ability to balance many genes in parallel is major outstanding challenge. Here, we introduce rapid modular method span expression space several proteins parallel. By combinatorially pairing with compact set ribosome-binding sites, modulate protein abundance by orders magnitude. We demonstrate our...