Biomolecular Pathways

Essential biological molecules—like proteins, lipids, RNA, and metabolites—translate the language of gene expression for the energy exchange and metabolism that leads to healthy cells, organisms, and living systems. The Environmental Molecular Sciences Laboratory (EMSL) Biomolecular Pathways Integrated Research Platform connects these biomolecules to their communication signals, biological roles, and functions to better explain and understand the trillions of small interactions that make up the world as we know it. This essential knowledge provides a fundamental understanding of molecular functions, bioprocesses, and metabolic pathways applicable for biomanufacturing and biotransformation, thus expanding the resource pool in bioeconomy activities. 

The science

The collective biomolecules in plants, fungi, algae, and bacteria determine an organism’s structure, function, and dynamics. EMSL has integrated capabilities to identify and quantify the functional components of complex systems uncovering the biomolecular pathways critical for important processes. Also, since many of the molecules in a biological system have not been identified, EMSL capabilities can be used to uncover the identity and function of these biological molecules through increasing the rate, dynamic range, and resolution by which we analyze proteins and metabolites. Our accelerated throughput—with integrated metabolomics, proteomics, and lipidomics—provides ultrasensitive measurements that explain the molecular mechanisms behind biological processes. With this capability, our research community explores biological complexity and diversity in the quest for more efficient bioproduct synthesis that will be critical in the emerging bioeconomy. 

How we do the science

EMSL’s Biomolecular Pathways expertise includes a breadth of cutting-edge capabilities. 

We combine advanced mass spectrometers, nuclear magnetic resonance (NMR) spectrometers, and statistics-driven data processing and integration to conduct high-throughput proteomic, metabolomic, and lipidomic analyses for biological discovery investigations providing comprehensive and integrated characterization of complex biological and environmental systems. 

• Combining quantitative bottom-up proteomics and top-down proteomic approaches yields an expanded quantitative survey of the protein complement and understanding of molecular assemblies. 
• We perform in-depth structure and function studies of intact proteins using high-resolution mass spectrometry (MS) and NMR spectroscopy. 

• Our combined approach using NMR spectroscopy and liquid chromatography-MS, gas chromatography-MS, and ion mobility spectrometry-MS yields greater metabolome coverage and more accurate metabolite identifications than any one technique alone. 
• Our MS imaging capabilities combine spatial, qualitative, and quantitative molecular information to study metabolites within specific locations. 

• We use mid-range scientific computing-based advanced data analytics and visualization software to more effectively translate large amounts of molecular measurements and multiomics data to essential biological understanding. 

Ultimately, these efforts will contribute to bolstering American manufacturing competitiveness and strengthening domestic supply chain security. 

Research in action

Understanding metabolic processes

When environments lack oxygen, syntrophic acetate oxidation (SAO) converts acetate into methane, relying on interactions between specific bacteria and methane-producing microorganisms. A research team led by the University of British Columbia conducted a 300-day study where they enriched a thermophilic SAO community, revealing how different microbes manage electron flow to improve the understanding of their metabolic processes in such systems. Using advanced techniques at EMSL, the team uncovered new quantitative applications of molecular biology tools to help predict the microbiomes that are important to biofuel production. 

Algae photosynthesis

Photosynthesis allows plants and algae to convert sunlight into energy and absorb carbon dioxide. When light and carbon dioxide availability changes, plants and algae adjust quickly through mechanisms that optimize photosynthesis and protect their cells. Over longer periods, they also make more permanent changes by adjusting their protein and metabolite levels to improve carbon capture and light use. A multi-institutional team of researchers led by the University of California, Berkeley, studied how the photosynthetic machinery in algae changes in response to environmental and nutritional variations. Using EMSL’s instrumentation and expertise, the team identified peptides from key photosynthetic proteins to determine the composition and quantities of photosynthetic complexes. Through increased knowledge of these complexes, the team gained a detailed understanding of how algae acclimate to changes in light and nutrient availability, including during the process of greening. This knowledge will be essential for optimizing photosynthesis in algae for biotechnological applications. 

Fungal research for bioproducts 

Converting sugar in filamentous fungi is a complex process involving multiple pathways. During growth on plant biomass, multiple 5- and 6-carbon monomeric sugars become simultaneously available to fungi. It is unknown whether fungi convert these sugars simultaneously or sequentially. There is also a lack of information about the conservation of catabolic pathways and the order that sugars are converted across the fungal kingdom. 

In a project led by Westerdijk Fungal Biodiversity Institute, researchers used EMSL’s mass spectrometry capabilities to investigate sugar conversion in fungi, particularly how these organisms use different sugars when breaking down plant material. Knowledge on sugar catabolism not only helps to understand the roles of these fungi in natural habitats but informs how to construct synthetic pathways for the production of bioinspired chemicals and materials.