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Systems Biology for Energy and the Environment

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Genomic Science Program

Systems Biology of Bioenergy-Relevant Microbes to Enable
Production of Next-Generation Biofuels and Bioproducts

Summary of Projects Awarded in 2021 under Funding Opportunity Announcement DE-FOA-0002448

September 2021

The U.S. Department of Energy’s (DOE) Genomic Science program, managed within the Office of Biological and Environmental Research (BER), supports basic research aimed at identifying the foundational principles that drive biological systems.GSP aims to solve critical challenges in energy security and environmental stewardship. As part of its mission, BER invests in crosscutting technologies and programs to enable multiscale, systems-level research to achieve a predictive understanding of systems biology, biological community function, and environmental behavior. BER aims to provide the necessary fundamental science to understand, predict, manipulate, and design biological processes that underpin innovations for bioenergy and bioproduct research and to enhance the understanding of natural environmental processes relevant to DOE. BER supports fundamental research to understand the systems biology of plants and microbes through the GSP. The GSP’s portfolio includes research that builds on a foundation of genomic data and combines experimental physiology studies with “omics”-driven tools of modern systems biology and computational approaches to harness the power of microorganisms and microbial communities as cellular factories. Through this portfolio of highly interdisciplinary and integrated research projects, the GSP aims to meet the challenges associated with microbial production of advanced biofuels and bioproducts from plant-derived biomass.

The ability to manipulate microbial biosynthetic pathways and metabolism using synthetic biology provides unprecedented opportunities to address a wide range of topics related to DOE’s mission in sustainable bioenergy development. This includes research that enhances the production of advanced biofuels and bioproducts, as well as the conversion and upcycling of synthetic polymers. To enable a future where biological systems can be designed and modified for desired specific outcomes and deliver positive impacts for the environment and the bioeconomy, the GSP solicited applications in two subtopic areas for this Funding Opportunity Announcement (FOA): sustainable bioenergy and polymer upcycling.

Subtopic A: Sustainable Bioenergy

The immense diversity and versatility of microbial metabolism offers the potential to sustainably produce bioenergy and bioproducts that are not dependent on fossil fuels. Realizing this potential requires a fundamental understanding of how biological systems behave. It is thus necessary to develop ways to design and control the functional capabilities within living systems to harness the biosynthetic processing power of the microbial world. The past decade has seen tremendous technological advances in the development of multiomics tools, high-throughput phenotypic screening approaches, and computational modeling methods to analyze, modify, and select specific functional properties of biological systems. Enhanced genomic biology capabilities allow for the development of pathways, strains, and microbial consortia to achieve novel chemistries, reduce barriers, and develop innovative solutions for biomass conversion. These advances, combined with new synthetic biology tools, provide an opportunity to help achieve DOE’s mission.

With the immense physiological and genetic diversity across the microbial world, there is potential to develop and engineer novel and model microorganisms with unique capabilities and biosynthetic pathways beyond what is currently used in industry. However, to engineer microorganisms to produce sustainable biofuels and bioproducts derived from lignocellulosic plant biomass or using carbon produced as a byproduct of photosynthesis, it is necessary to improve our understanding of microbial physiology and metabolism. It is also imperative to determine how to efficiently shunt precursors and intermediates from central metabolism into complex products while rebalancing organismal carbon allocations. Systems biology-driven approaches will build on the understanding of these processes to design new pathways and tools for biofuels and bioproducts.

This subtopic specifically targeted systems biology-driven basic research for the production of advanced biofuels (i.e., biologically synthesized compounds with the potential to serve as energy dense transportation fuels such as gasoline, diesel, and aviation fuel) compatible with existing engines and fuel distribution infrastructure, and for the production of useful bioproducts. In this context, the following areas were of interest:

  • Developing emerging model microorganisms and/or microbial communities with unique or enhanced capabilities to produce advanced biofuels and/or bioproducts. Proposed studies may 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 or environmental signal processing related to product synthesis, (3) improving fundamental understanding of integrated function and compatibility of novel enzyme systems within the microbe or microbial community with direct applicability to lignocellulose breakdown or advanced biofuels and/or bioproducts production, and (4) further developing genetic tools to facilitate study and manipulation of microbial species for which genomic information is available and a genetic system is at least in its initial stages of development.
  • Understanding novel microbial functional capabilities and biosynthetic pathways relevant to the production of advanced biofuels and bioproducts. Proposed research should include the development of strategies to identify and overcome metabolic impacts that result from pathway modification and limit production of target molecules. Proposed studies could include but are not limited to (1) developing robust and efficient pathways for advanced biofuels and bioproducts synthesis, (2) identifying functional processes involved in deconstruction of lignocellulosic plant material, (3) elucidating and modifying phenotypes involved in enhanced strain tolerance to stresses relevant to biofuel and bioproduct production, and (4) developing methods to overcome problems with recombinant expression of vital enzymes and pathways.

Subtopic B: Polymer Upcycling

Globally, more than 350 million metric tons of plastic polymers are produced annually, and their production is anticipated to quadruple by 2050. As much as three quarters of this material is single use, and only a small proportion is currently recycled. Key difficulties, such as separating mixed waste streams and the need for high temperatures or specialized catalysts for their conversion to usable chemical forms, present important economic disincentives for recycling. Discarding plastics into landfills wastes the energy equivalent of tens of billions of dollars annually and creates a long-term, unsustainable waste legacy. Biological solutions for polymer upcycling may offer unique advantages over traditional thermal cracking and catalyst-based approaches by allowing processing at ambient temperatures, eliminating the need for specialized metal catalysts, and potentially reducing capital investment. However, biological solutions for the breakdown of most synthetic polymers are currently unavailable, representing an important knowledge gap and basic research opportunity.

BER intends to build on rapid advances in genomic science, biosystems design, and computational biology to develop enhanced capabilities for biologically based polymer recycling. BER seeks to apply principles of genome engineering and microbiome science to deconstruct polymers and/or to convert polymer waste streams to usable monomers for new materials. Though synthetic polymers are typically considered to be highly recalcitrant to biological depolymerization, evidence indicates that some plastics, such as polyethylene terephthalate (PET) and ester-based polyurethanes, can be enzymatically deconstructed. However, enzymatic pathways for the depolymerization of many other polymers, such as polystyrene, polyamides, or ether-based substrates, remain unknown. Leveraging the tools of synthetic and computational biology may provide opportunities to redesign metabolic pathways in established or emerging model organisms and/or within complex communities to depolymerize difficult synthetic substrates. Both known and novel biochemical pathways and methods for deconstruction and conversion to new products were of interest.

This subtopic specifically targeted synthetic biology and omics-driven basic research on the bioconversion and reuse of synthetic polymers in the following areas:

  • Identifying and developing novel biological mechanisms, enzymes, and pathways for polymer deconstruction and conversion in both model and environmental microbes. Applications should focus on the elucidation of novel enzymes and biochemical pathways for polymer breakdown. This may include studies in model organisms or complex consortia. Experiments should aim to use a systems approach to understand the metabolic, biochemical, regulatory, and genetic basis of specific and defined activities.
  • Designing new biosynthetic pathways for the conversion of polymers into new products or their precursors. Studies should leverage the tools of computational and systems biology to design novel pathways or approaches for polymer degradation and conversion to higher value waste streams. An important focus of this FOA is to expand the range of products that can be produced biologically from recycled polymers.

In conjunction with research addressing the two subtopics outlined above, applicants could propose use-inspired basic research to develop analytical technologies to better understand how to evaluate and characterize relevant functional processes or how high-throughput phenotyping capabilities can be used to evaluate modified biofuel producing strains to enhance the design, build, test, and learn cycle, as long as the applica­tions were tightly integrated with the stipulated subtopics.

2021 Awards

Energy and Carbon Optimized Conversion of Lignocellulose to Biobased Chemicals by Extreme Thermophiles

Converting Methoxy Groups on Lignin-Derived Aromatics from a Toxic Hurdle to a Useful Resource: A Systems-Driven Approach

Cell-Free Systems Biology of an Atypical Glycolytic Pathway

Engineering Synthetic Anaerobic Consortia Inspired by the Rumen for Biomass Breakdown and Conversion

A Gene-Editing System for Large-Scale Fungal Phenotyping in a Model Wood Decomposer

Developing, Understanding, and Harnessing Modular Carbon/Nitrogen-Fixing Tripartite Microbial Consortia for Versatile Production of Biofuel and Platform Chemicals

  • Principal Investigator: Nina Lin (University of Michigan)

Metabolic Modeling and Genetic Engineering of Enhanced Anaerobic Microbial Ethylene Synthesis

  • Principal Investigator: Justin North (The Ohio State University)
  • Collaborator: William Cannon (Pacific Northwest National Laboratory)

Quantitative Analysis of Metabolic Segregation of Lignin Deconstruction and Catabolism in Outer Membrane Vesicles of Soil Pseudomonas species

Optogenetic Control of Microbial Consortia for Biofuel and Chemical Production

  • Principal Investigator: Jose Avalos (Princeton University)

Systems Biology to Enable Modular Metabolic Engineering of Fatty Acid Production in Cyanobacteria

  • Principal Investigator: Jamey Young (Vanderbilt University):

Novel Systems Approach for Rational Engineering of Robust Microbial Metabolic Pathways

Synthetic Metabolic Pathways and Biosensors to Expand Lignin-Based Bioconversion

  • Principal Investigator: Ellen Neidle (University of Georgia)
  • Collaborator: Ramesh Jha (Los Alamos National Laboratory)

The Whole is Greater than the Sum of Its Parts: Multi-Scale Modeling and Engineering of Microbial Communities for Next-Generation Bioproduction

  • Principal Investigator: Karsten Zengler (University of California, San Diego)
  • Collaborator: Michael Guarnieri (National Renewable Energy Laboratory)

Harnessing the Robust Metabolism of Bacillus coagulans for Efficient Conversion of Lignocellulosic Biomass Hydrolysates to Designer Bioesters

  • Principal Investigator: Cong Trinh (University of Tennessee)
  • Collaborators: Richard Giannone (Oak Ridge National Laboratory) and Bruce Dien (USDA Agricultural Research Service)

Improving Bioprocess Robustness by Cellular Noise Engineering

  • Principal Investigator: Gregory Stephanopoulos (Massachusetts Institute of Technology)

Engineering Bacterial Microcompartments in Clostridium autoethanogenum to Overcome Bottlenecks in Sustainable Production of Synthetic Rubber

  • Principal Investigator: Danielle Tullman-Ercek (Northwestern University)

Optimizing Enzymes for Plastic Upcycling Using Machine Learning Design and High Throughput Experiments

  • Principal Investigator: Nicholas Gauthier (Dana-Farber Cancer Institute)
  • Collaborator: Gregg Beckham (National Renewable Energy Laboratory)

Novel Enzymes and Synthetic Metabolic Pathways for Complete Degradation and Upcycling of Recalcitrant Polyamides

  • Principal Investigator: Alexandre Zanghellini (Arzeda Corporation)

Discovery of Distributed Pathways for Plastic Conversion in the Yellow Mealworm Microbiome

  • Principal Investigator: Kevin Solomon (University of Delaware)
  • Collaborator: Aaron Wright (Pacific Northwest National Laboratory)

Developing a Consolidated Biological Process to Upcycle Plastics

  • Principal Investigator: Tae Seok Moon (Washington University)

SynThetic BiolOgy Driven Approach to Repurpose PolyaMides (STORM)

  • Principal Investigator: Kate Kucharzyk (Battle Memorial Institute)
  • Collaborator: Jaydeep Bardhan (Pacific Northwest National Laboratory)


For More Information

BER Program Managers for Systems Biology

Dawn Adin
U.S. Department of Energy
Office of Biological and Environmental Research
Phone: 301-903-9549

Dr. Boris Wawrik
U.S. Department of Energy
Office of Biological and Environmental Research
Phone: 301-903-4742



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