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Birgit Alber
alber.8@osu.edu
B.S. Biology equivalent, University of Marburg
PhD. Anaerobic Microbiology, Virginia Tech
Postdoctoral research, University of Freiburg |
Assistant Professor of Microbiology
Biochemistry of central carbon metabolism
Purple non-sulfur bacteria are some of the metabolically most versatile organisms known. Rhodobacter sphaeroides, Rhodospirillum rubrum, Rhodopseudomonas palustris, etc.are capable of using a variety of modes for energy conservation: they either utilize light as an energy source (under anoxic conditions) or organic and inorganic compounds as electron donors and acceptors (respiratory and fermentative growth). This remarkable metabolic versatility of non-sulfur purple bacteria extends to the utilization of a large spectrum of carbon sources, ranging from carbon dioxide (autotrophic growth) to fermentative products generated by other organisms in the same habitats.
R. sphaeroides has been studied extensively in several aspects of metabolism, the organism is genetically accessible, and the sequence of its genome is available. This then provides an excellent opportunity to uncover novel metabolic routes involving unique carbon transformations using R. sphaeroides as a model organism.
Acetyl-CoA assimilation
Growth on organic substrates that are metabolized via acetyl-CoA (such as fatty acids, alcohols, and esters, including various fermentation products, but also waxes, alkenes, taurine, and methylated compounds) requires the synthesis of all cell constituents from this C2-unit. Fifty years ago Kornberg and Krebs established the glyoxylate cycle as an anaplerotic reaction sequence for the citric acid cycle, allowing cell carbon biosynthesis from acetyl-CoA (May 18, 1957; Nature 17: 988 – 991). Recently we described the ethylmalonyl-CoA pathway for assimilation of acetyl-CoA in the absence of a functional glyoxylate cycle. (Alber et al., 2006, Erb et al., 2007).
The key enzyme of the ethylmalonyl-CoA pathway is a novel carboxylase catalyzing the reductive carboxylation of an enoyl-CoA substrate: crotonyl-CoA carboxylase/reductase. The enzyme, for which the catalytic mechanism is under investigation, connects the C4 and C5-branch are also unique. We use biochemical and genetic approaches to elucidate and study the individual enzymatic reactions involved.
Reactions of the ethylmalonyl-CoA pathway also provide the extender units for the biosynthesis of several antibiotics by polyketide synthases in actinomycetes. For methylotrophic bacteria such as Methylobacterium extorquens extension of the serine cycle with reactions of the ethylmalonyl-CoA pathway leads to a simplified scheme for isocitrate lyase-independent C1 assimilation.
Ethylmalonyl-CoA Pathway (Acetyl-CoA Assimilation)
Erb, T. J., G. Fuchs, B. E. Alber. 2009. (2S)-Methylsuccinyl-CoA dehydrogenase closes the ethylmalonyl-CoA pathway for acetyl-CoA assimilation. Mol. Microbiol. 73:992-1008. Comments in Mol. Microbiol.
Erb, T. J., V. Brecht, G. Fuchs, M. Müller, and B. E. Alber. 2009. Carboxylation mechanism and stereochemistry of crotonyl-CoA carboxylase/reductase, a carboxylating enoyl-thioester reductase. Proc. Natl. Acad. Sci. U.S.A. 106:8871-8876.
Erb, T. J., J. Rétey, G. Fuchs, and B. E. Alber. 2008. Ethylmalonyl-CoA mutase from Rhodobacter sphaeroides defines a new subclass of coenzyme B12-dependent acyl-CoA mutases. J. Biol. Chem. 283:32283-32293.
Erb, T. J., I. A. Berg, V. Brecht, M. Müller, G. Fuchs, and B. E. Alber. 2007. Synthesis of C5-dicarboxylic acids from C2 units involving crotonyl-CoA carboxylase/reductase: The ethylmalonyl-CoA pathway. Proc. Natl. Acad. Sci. U.S.A. 104:10631-10636. Comments in Faculty 1000.
Alber, B. E., R. Spanheimer, C. Ebenau-Jehle, and G. Fuchs. 2006. Study of an alternate glyoxylate cycle for acetate assimilation by Rhodobacter sphaeroides. Mol. Microbiol. 61:297-309. Comments in Faculty 1000, Mol. Microbiol.
Meister, M., S. Saum, B. E. Alber, and G. Fuchs. 2005. L-Malyl-coenzyme A/beta-methylmalyl-coenzyme A lyase is involved in acetate assimilation of the isocitrate lyase-negative bacterium Rhodobacter capsulatus. J. Bacteriol. 187:1415-1425.
CO2 Fixation (3-Hydroxypropionate Cycle)
B. E. Alber, J. W. Kung, and G. Fuchs. 2008. 3-Hydroxypropionyl-coenzyme A synthetase from Metallosphaera sedula, a n enzyme involved in autotrophic CO2 fixation. J. Bacteriol. 190:1383-1389.
Zarzycki, J., A. Schlichting, N. Strychalski, M. Müller, B. E. Alber, G. Fuchs. 2008. Mesaconyl-coenzyme A hydratase, a new enzyme of two central carbon metabolic pathways in bacteria. J. Bacteriol. 190:1366-1374.
Alber, B. E., and G. Fuchs. 2002. Propionyl-coenzyme A synthase from Chloroflexus aurantiacus, a key enzyme of the 3-hydroxypropionate cycles for autotrophic CO2 fixation. J. Biol. Chem. 277:12137-43.
Gamma Carbonic Anhydrase
Iverson, T. M., B. E. Alber, C. Kisker, J. G. Ferry, and D. C. Rees. 2000. Closer look at the active site of gamma-carbonic anhydrase: high resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila. Biochemistry 39:9222-9231.
Alber, B. E., C. M. Colangelo, J. Dong, C. M. V. Stålhandske, T. T. Baird, C. Tu, C. A. Fierke, D. N. Silverman, R. A. Scott, and J. G. Ferry. 1999. Kinetic and spectroscopic characterization of the gamma carbonic anhydrase from the methanoarchaeon Methanosarcina thermophila. Biochemistry 38:13119-13128.
Alber, B. E., and J. G. Ferry. 1994. A carbonic anhydrase from the archaeon Methanosarcina thermophila. Proc. Natl. Acad. Sci. U.S.A. 91:6909-6913.
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