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Microbial powerhouses harness cellular energy fluctuations for bioproduction

By Brian Buntz | July 8, 2024

ATP biosensor

The illuminated green areas in this image of E. coli are indicators of Adenosine-5’-triphosphate (ATP). In the research described here, an ATP biosensor enables researchers to track ATP levels and how it affects yields of the chemicals produced by the microbe. [Photo: Zhang lab]

Engineers at Washington University in St. Louis are tapping microorganisms to produce sustainable fuels, chemicals, materials, and medicines. Their latest research, published in Nature Communications, focuses on the role of ATP (adenosine-5′-triphosphate) in microbial metabolism and its role on bioproduction.

Recognizing that ATP, the primary cellular energy currency, fluctuates significantly in microbes used for biomanufacturing, the team, led by Fuzhong Zhang, a professor of energy, environmental and chemical Engineering, developed a genetically encoded ATP biosensor. This tool allowed the researchers to track real-time changes in ATP levels within living microbes under various fermentation conditions, providing new insight into how these tiny biological factories manage energy resources.

Impact on both ATP dynamics and product yield

uzhong Zhang and PhD student Xinyue Mu

Professor Fuzhong Zhang and PhD student Xinyue Mu look over microscope images of E. coli used in bioproduction. [Photo: Leah Shaffer/Washington University]

Armed with this biosensor, the researchers explored how different carbon sources (the food microbes consume) impact ATP levels in two workhorse microbes: Escherichia coli and Pseudomonas putida. They found that carbon source selection significantly affects both ATP dynamics and the yield of desired products.

Key findings include:

  1. Different carbon sources drive distinct ATP dynamics in microbes, with each leading to unique patterns of ATP level changes during different growth phases.
  2. In E. coli, acetate, often considered a waste byproduct, led to the highest ATP levels and a 2.7-fold increase in fatty acid production compared to other tested carbon sources.
  3. For P. putida, oleate was identified as the optimal carbon source, significantly enhancing the production of polyhydroxyalkanoates (PHAs), a type of biodegradable bioplastic.

Practical applications

By providing a window into real-time ATP dynamics, the biosensor could pave the way to new strategies for optimizing microbial production systems. Similar to how athletes optimize diets for peak performance, this research demonstrates the power of tailoring microbial “diets” for enhanced bioproduction. The study revealed that seemingly subtle changes in carbon source dramatically impact ATP levels and product yields.

For example, supplementing E. coli with acetate, a common waste product, led to surprisingly high ATP levels and a 2.7-fold increase in fatty acid production. This upcycling approach, described in the Nature paper as taking advantage of “acetate’s unique metabolic characteristics,” points to new approaches to transform waste streams into valuable precursors for biofuels and other chemicals.

Similarly, the study highlights the benefits of using oleate, a fatty acid, as a feedstock for P. putida. Oleate significantly increased ATP levels and boosted the production of polyhydroxyalkanoates (PHAs), a biodegradable bioplastic, highlighting the potential for sustainable bioplastic manufacturing from renewable resources.

As the paper concludes, this work “not only illuminates the complex relationship between ATP dynamics and bioproduction but also offers a simple and effective strategy to enhance biomanufacturing systems for a more sustainable future.”

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