Gene sequence analysis and computer modeling to identify and screen new proteins

BEEM researchers will sequence microbial cultures and enzymes that result from lab reserach in fermentation and biodegradation, and will also work with existing genomic libraries.  This work results in large-scale genomic "parts lists" and making sense of these enormous datasets requires the use of sophisticated computational tools.  The aim is to use bioinformatics methods on the sequencing data to construct a model of exactly what is going on at a cellular and molecular level within the cultures, i.e. to get a clear picture of the metabolism and cell interactions involved in the processes of interest.  This will allow researchers to discover new enzymatic pathways and will suggest ways to optimize the desired microbial activities.  The BEEM team includes metabolic modeling experts who are leaders in this field and will develop and apply new bioinformatics tools to extract meaning from these large metagenomic datasets.

The first step in this process is the analysis and annotation of metagenomic sequence data.  Next, computer models of metabolic networks are constructed based on sequence similarity, physiology and biochemical information from the whole community and enzyme screens.  The reconstructed network is then used to develop genome-scale models of whole community function as well as pathway-specific models.  These models elucidate the metabolic capabilities of the community and how to optimize these microbial cultures and enzymes.  This work will be useful for:

  1. visualization and mining gene expression data
  2. identification and reconstruction of novel metabolic pathways responsible for the cultures' observed biotransformation activity
  3. identification of imporatnt metabolic interactions between members of the microbial community
  4. optimization of the culture's activity through the addition of either substrates that promote growth or other organisms that provide these substrates

Metabolic models will help to identify the individual metabolic reactions that may not be detected in the enzyme screens, but are required for the overall culture activity.  This information will feed back to the lab by suggesting ways to optimize the cultures' performance that can be tested in microcosms.  At the same time, the models will be continuously refined based on the biochemical and physiological studies performed in the lab.  Ultimately, this framework will enable the a priori prediction of novel biotransformation capabilities of the cultures, identify the optimal consortia with the desired activities, and facilitate the development of viable bioproducts and bioprocesses.


Sequence- and activity-based screening of microbial genomes for novel dehalogenases. Chan, W. Y., Wong, M., Guthrie, J., Savchenko, A. V., Yakunin, A. F., Pai, E. F., and E. A. Edwards
EMILiO: A fast algorithm for genome-scale strain design Yang, L., Cluett, W.R., and R. Mahadevan
Economics of membrane occupancy and respiro-fermentation Zhuang, K., Vemuri, G.N., and R. Mahadevan
Localized plasticity in the streamlined genomes of vinyl chloride respiring Dehalococcoides. McMurdie, P. J., Behrens, S. F., Mueller, J. A., Goeke, J., Ritalahti, K. M., Wagner, R., Goltsman, E., Lapidus, A., Holmes, S., Loeffler, F. E., and A. M. Spormann
Genome-scale dynamic modeling of the competition between Rhodoferax and Geobacter in anoxic subsurface environments. Zhuang, K., Izallalen, M., Mouser, P., Richter, H., Risso, C., Mahadevan, R., and D. R. Lovley
Single residues dictate the co-evolution of dual esterases: MCP hydrolases from the α/β hydrolase family Alcaide, M., Tornes, J., Stogios, P.J., Xu, X., Gertler, C., Di Leo, R., Bargiela, R., Lafraya, A., Guazzaroni, M.E., Lopez-Cortes, N., Chernikova, T.N., Golyshina, O.V., Nechitaylo, T.Y., Plumeier, I., Pieper, D.H., Yakimov, M.M., Savchenko, A., Golyshin, P.N., and M. Ferrer
Genome sequence and functional genomic analysis of the oil-degrading bacterium Oleispira antarctica Kube, M., Chernikova, T.N., Al-Ramahi, Y., Beloqui, A., Lopez-Cortez, N., Guazzaroni, M.E., Heipieper HJ, Klages S, Kotsyurbenko OR, Langer, I., Nechitaylo, T.Y., Lünsdorf, H., Fernández, M., Juárez, S., Ciordia, S., Singer, A., Kagan, O., Egorova, O., Alain Petit, P., Stogios, P., Kim, Y., Tchigvintsev, A., Flick, R., Denaro, R., Genovese, M., Albar, J.P., Reva, O.N., Martínez-Gomariz, M., Tran, H., Ferrer, M., Savchenko, A., Yakunin, A.F., Yakimov, M.M., Golyshina, O.V., Reinhardt, R., and P.N. Golyshin
Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutieres Syndrome and HIV-1 Restriction Beloglazova, N., Flick, R., Tchigvintsev, A., Brown, G., Popovic, A., Nocek, B., and A.F. Yakunin
Biochemical diversity of carboxyl esterases and lipases from Lake Arreo -- a metagenomic approach Martínez-Martínez, M., Alcaide, M., Tchigvintsev, A., Reva, O., Polaina, J., Bargiela, R., Guazzaroni, M.E., Chicote A, Canet A, Valero F, Eguizabal, E.R., Guerrero, M.D., Yakunin, A.F., and M. Ferrer