Systems Biology–Enabled Research for Microbial Production of Advanced Biofuels

The U.S. Department of Energy’s (DOE) Genomic Science program, managed within the Office of Biological and Environmental Research (BER), supports fundamental research to identify the foundational principles that drive biological systems. These principles govern translation of the genetic code into integrated networks of proteins, enzymes, regulatory elements, and metabolite pools underlying the functional processes of organisms. To address DOE’s mission in sustainable bioenergy development, the Genomic Science program applies “omics”-driven tools of modern systems biology to challenges associated with microbial production of advanced biofuels.

Developing an increased understanding of how biological systems function and translating that knowledge to enhance the production capabilities of microbes and plants forms the basis of DOE’s mission in sustainable bioenergy. To harness the microbial world’s biosynthetic processing power for advanced biofuels production, an expanded set of platform organisms is needed with appropriate metabolic capabilities and stress tolerance characteristics. The DOE BER Genomic Science program supports research aimed at improving fundamental understanding of principles that govern the functional properties of bioenergy-relevant organisms at the genome scale. This knowledge will enable development of molecular genomics approaches and computational tools for the design, construction, and validation of improved biological components and systems. This highly interdisciplinary endeavor spans multiple fields in biology, systems biology, chemical and metabolic engineering, and computational biology

Significant progress in the last decade has increased understanding of biological systems and the capabilities for manipulating them. These advances result largely from the tremendous technological leaps in developing molecular biology tools (e.g., genomic, metabolomic, and proteomic tools) to analyze and modify the functional properties of biological systems. Despite these advances, many fundamental gaps remain in understanding microbial metabolism and physiology related to the production of sustainable, efficient, and economically competitive biofuels derived from lignocellulosic plant biomass or from photosynthetic capture of carbon dioxide (CO₂).

The 2014 Funding Opportunity Announcement described herein specifically targets production of advanced biofuels, which in this context refers to biologically synthesized compounds with the potential to serve as energy-dense transportation fuels (e.g., diesel, gasoline, and aviation fuels) compatible with existing engines and fuel distribution infrastructures. Advanced biofuels production requires significant progress in the basic understanding of microbial metabolism and the conversion of photosynthetically derived carbon compounds (either via direct photosynthesis or acquired via breakdown of lignocellulosic plant biomass). Another goal is to determine how products can be efficiently shunted from central metabolism into complex products with associated rebalancing of organismal carbon allocations and redox potential.

BER solicited applications for systems biology–driven basic research in three areas of development focused on enabling advanced biofuels production:

• Promising new model organisms relevant to biofuels production. Proposed studies could include but are not limited to (1) advancing systems biology understanding and predictive modeling of specialist microbes or microbial consortia, (2) elucidating relevant regulatory and metabolic networks involved in product synthesis or environmental signal processing, (3) improving fundamental understanding of integrated function and compatibility of novel enzyme systems with direct applicability to lignocellulose breakdown or advanced biofuels production, and (4) developing genetic tools to facilitate study and manipulation of genetically intractable species
• Novel microbial functional capabilities and biosynthetic pathways relevant to advanced biofuels production and strategies to overcome associated metabolic challenges resulting from pathway modification. Proposed studies could include but are not limited to (1) development of robust and efficient pathways for advanced biofuels synthesis, (2) functional processes involved in deconstructing lignocelluosic plant material, (3) elucidation and modification of phenotypes involved in tolerance to stresses relevant to biofuels production, and (4) development of methods to overcome problems with recombinant expression of vital enzymes and pathways.
• Novel analytical technologies or high-throughput screening approaches. In conjunction with research addressing the two previously outlined topic areas, investigators may propose the development of analytical technologies facilitating characterization of relevant functional processes or high-throughput phenotyping of modified biofuel-producing strains. Only proposals for technology development tightly integrated with research addressing the two preceding topics will be considered.