Daniel Amador-Noguez
University of Wisconsin-Madison, WI·Microbiology & Immunology
Turning plant waste into fuel depends on microbes that can both chew up tough plant material and survive the alcohol they make. Both steps are poorly understood at the level of cell chemistry.
- Fields
Microbiology & Immunology
Biochemistry
Engineering
- Topics
Clostridium thermocellum
ethanol tolerance
alcohol toxicity
- Grants
- 2 known grants, through Sep 2029
What they work on
- Test whether alcohol dehydrogenase (AdhE) activity raises the NADH/NAD+ ratio enough to block glycolysis in Clostridium thermocellum, using metabolomics, isotope tracing of labeled sugars, and targeted genetic knockouts.
- Determine how cofactor preference (NADH versus NADPH) in alcohol dehydrogenases shapes ethanol tolerance, combining adaptive laboratory evolution with rational strain engineering.
- Quantify how much metabolite leaks across the membrane at different ethanol concentrations and how membrane lipid composition adapts, using lipidomics and biophysical measurements.
- Integrate metabolic and membrane data into a concentration-stratified model that specifies which toxicity mechanism dominates at each ethanol level and yields design rules for solvent-tolerant strains.
- Characterize substrate transport and the reversibility of central metabolic reactions in C. thermocellum to identify what restricts the range of sugars it can grow on.
- Identify mutations enabling growth on alternative substrates via stationary-phase evolution and combinatorial multi-substrate chemostats, then use those substrates to pinpoint what limits ethanol titer.
More about the research
Two projects dig into the metabolism of Clostridium thermocellum, a heat-loving bacterium that breaks down plant fiber and ferments it directly into ethanol, to find out what limits how much product it can make and how much alcohol it can tolerate.
Why it matters
More than 32 billion gallons of ethanol are produced each year, mostly from starch and sugar crops. Shifting to cellulosic feedstocks such as agricultural waste and wood would make fuel production cheaper and more sustainable, but it requires microbes that survive the alcohol they generate. Identifying the true cause of alcohol toxicity could give metabolic engineers concrete design rules for more tolerant, higher-yielding strains, and the methods extend to other microbially produced chemicals.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
John G. Albeck
University of California-Davis, CA·Biology
Use multiplexed live-cell sensors to constrain mathematical models of how glycolysis rates vary across single cells, and identify the smallest, most informative set of measurements.
Karthikeyani Chellappa
Brown University, RI·Biochemistry
Define how nicotinamide (NAM), the main NAD building block, crosses the plasma membrane of mammalian cells through the biphasic transport system the lab discovered.
Isaac Marin-Valencia
Icahn School of Medicine at Mount Sinai, NY·Neuroscience
Determine when two proposed metabolic switches start and how long they last in the developing mouse brain: glycolysis to oxidative metabolism, and the propionate-to-succinyl-CoA pathway to pyruvate carboxylation. The project will use 13C isotope tracing.
The school
University of Wisconsin-Madison: 91 labs on PI Pages, $1.9B a year on research, 854 research doctorates a year.
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