ECUT (Energy Conversion and Utilization Technologies Program). Biocatalysis Project

Presented are the FY 1985 accomplishments, activities, and planned research efforts of the Biocatalysis Project of the U.S. Department of Energy, Energy Conversion and Utilization Technologies (ECUT) Program. The Project's technical activities were organized as follows: In the Molecular Modeling and Applied Genetics work element, research focused on (1) modeling and simulation studies to establish the physiological basis of high temperature tolerance in a selected enzyme and the catalytic mechanisms of three species of another enzyme, and (2) determining the degree of plasmid amplification and stability of several DNA bacterial strains. In the Bioprocess Engineering work element, research focused on (1) studies of plasmid propagation and the generation of models, (2) developing methods for preparing immobilized biocatalyst beads, and (3) developing an enzyme encapsulation method. In the Process Design and Analysis work element, research focused on (1) further refinement of a test case simulation of the economics and energy efficiency of alternative biocatalyzed production processes, (2) developing a candidate bioprocess to determine the potential for reduced energy consumption and facility/operating costs, and (3) a techno-economic assessment of potential advancements in microbial ammonia production

Archiving and disseminating integrative structure models.

Limitations in the applicability, accuracy, and precision of individual structure characterization methods can sometimes be overcome via an integrative modeling approach that relies on information from all available sources, including all available experimental data and prior models. The open-source Integrative Modeling Platform (IMP) is one piece of software that implements all computational aspects of integrative modeling. To maximize the impact of integrative structures, the coordinates should be made publicly available, as is already the case for structures based on X-ray crystallography, NMR spectroscopy, and electron microscopy. Moreover, the associated experimental data and modeling protocols should also be archived, such that the original results can easily be reproduced. Finally, it is essential that the integrative structures are validated as part of their publication and deposition. A number of research groups have already developed software to implement integrative modeling and have generated a number of structures, prompting the formation of an Integrative/Hybrid Methods Task Force. Following the recommendations of this task force, the existing PDBx/mmCIF data representation used for atomic PDB structures has been extended to address the requirements for archiving integrative structural models. This IHM-dictionary adds a flexible model representation, including coarse graining, models in multiple states and/or related by time or other order, and multiple input experimental information sources. A prototype archiving system called PDB-Dev ( https://pdb-dev.wwpdb.org ) has also been created to archive integrative structural models, together with a Python library to facilitate handling of integrative models in PDBx/mmCIF format

Metabolic flux understanding of Pichia pastoris grown on heterogenous culture media

[EN] Within the emergent field of Systems Biology, mathematical models obtained from physical chemical laws (the so-called first principles-based models) of microbial systems are employed to discern the principles that govern cellular behaviour and achieve a predictive understanding of cellular functions. The reliance on this biochemical knowledge has the drawback that some of the assumptions (specific kinetics of the reaction system, unknown dynamics and values of the model parameters) may not be valid for all the metabolic possible states of the network. In this uncertainty context, the combined use of fundamental knowledge and data measured in the fermentation that describe the behaviour of the microorganism in the manufacturing process is paramount to overcome this problem. In this paper, a grey modelling approach is presented combining data-driven and first principles information at different scales, developed for Pichia pastoris cultures grown on different carbon sources. This approach will allow us to relate patterns of recombinant protein production to intracellular metabolic states and correlate intra and extracellular reactions in order to understand how the internal state of the cells determines the observed behaviour in P. pastoris cultivations.Research in this study was partially supported by the Spanish Ministry of Science and Innovation and FEDER funds from the European Union through grants DPI2011-28112-C04-01 and DPI2011-28112-C04-02. The authors are also grateful to Biopolis SL for supporting this research. We also gratefully acknowledge Associate Professor Jose Camacho for providing the Exploratory Data Analysis Toolbox.González Martínez, JM.; Folch-Fortuny, A.; Llaneras Estrada, F.; Tortajada Serra, M.; Picó Marco, JA.; Ferrer, A. (2014). Metabolic flux understanding of Pichia pastoris grown on heterogenous culture media. Chemometrics and Intelligent Laboratory Systems. 134:89-99. https://doi.org/10.1016/j.chemolab.2014.02.003S899913

Fermentation: Metabolism, Kinetic Models, and Bioprocessing

Biochemical and metabolic interpretation of microbial growth is an important topic in bioreactor design. We intend to address valuable information about the relation of critical operation variables and the simulation of bioprocesses with unstructured and structured kinetic models. Process parameters such as nutrient supply, pH, dissolved oxygen, and metabolic end-products directly impact the physiology and metabolism of microorganisms. Changes in the membrane as well as cell viability are of interest since protein expression and maturation in prokaryota are directly related to membrane integrity. This chapter intends to deliver an insight of different alternatives in kinetic modeling

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 130, July 1974

This special bibliography lists 291 reports, articles, and other documents introduced into the NASA scientific and technical information system in June 1974