Fueling the Future: How Microbes Will Power the Bioeconomy

Fueling the Future: How Microbes Will Power the Bioeconomy

From scents to solvents, fuels to fertilizers, the world runs on chemicals. Many of the compounds underlying the humdrum of civilization are unsustainable (e.g., fossil resources) and destructive to both people and the planet. Finding alternatives that are replenishable, mitigate risks and limit (or, better yet, clean up) environmental and atmospheric pollution requires thinking big—and bitty.

Fossil Fuels Are Dwindling, Microbes Can Help

A service station gasoline pump with black, green and yellow handles. Despite being a limited resource with harmful environmental effects, fossil fuels make up a majority of the fuels used to power society.
Source: iStock.com/mladenbalinovac.
Society is powered by the chemical remnants of prehistoric, organismic death (i.e., fossil fuels). Here’s the problem: fossil fuels are finite, they are drivers of climate change, and, despite the preceding facts in this list, they are everywhere (96% of transportation fuels worldwide are fossil resources). This dependence on a diminishing fuel source is a conundrum that scientists think biofuels—those derived from or produced by living organisms, like plant and microbial biomass—could help solve. “Renewable energy is our future,” said Bing-Jie Ni, Ph.D., a professor of civil and environmental engineering at University of South Wales. “And I think biomass is one of the key pathways for producing renewable energy because it is so abundant on Earth."

Expanding the global biofuel landscape is a massive endeavor, with microbes as central characters. But leveraging microbial life to produce biofuel is both forward-thinking and old news. The 10% ethanol added to gasoline to improve engine performance and reduce greenhouse gas emissions? Most of that is generated via fermentation of plant material by the yeast Saccharomyces cerevisiae. Feedstock fermentation by Clostridia bacteria yields butanol, another alcohol blended into gasoline, as well as used to generate plastics, solvents, fibers and more. These gasoline mixers are well-integrated into the current fuel economy. The future, however, will include harnessing the fuel-generating powers of microbes in new, more comprehensive ways.

Algae: A Rich Source of Fuel Precursors

Microscopic view of microalgae; the cells are round and dark green. Algae are rich in biofuel precursors, and can be used to produce fuels like biodiesel.
Source: Flickr.
Take algae as an example. Among the many microbes with biofuel-producing potential, including cyanobacteria, fungi and yeasts, these photosynthetic organisms are near the front of the pack. Part of their appeal is that algae are physiologically rich in extractable biofuel precursors. In a sense, algae are not simply metabolic workhorses, they are also biofuel feedstocks themselves.

Ni’s lab is exploring how to use algae to produce high-value biofuel building blocks, specifically medium chain carboxylic acids (MCCAs) and alcohols. There is no current pathway for large-scale production of MCCAs. This is a desirable goal, however, as MCCAs are more easily processed than related fuel-precursors and have additional applications as additives in agricultural feedstocks and pharmaceuticals. Algae could be the way forward.

“We are currently looking at different operational conditions to regulate the process and produce more alcohol or MCCA,” Ni shared. He and his team recently found that altering the pH in algae fermentation reactions changed the products the algae generated—a higher pH led to a greater abundance of MCCAs, while lower pH resulted in more alcohols. These findings will be useful for customizing the fermentation process “to produce the products you want,” Ni noted, highlighting that the lab has also looked at how factors like temperature and microbial community structure and function influence product generation.

From a bioeconomic standpoint, there is a lot to love about algae. For one, they are more energy-dense than conventional crops: if corn can yield 600 L/hectare/year of ethanol, algae fermentation can produce 15 times that. Moreover, unlike fossil resources, algae do not add new carbon into an already overloaded atmosphere. Instead, they use atmospheric carbon to grow. Combustion of fuel derived from algae (and other biomass) releases that same carbon back into the environment.

In Ni’s eyes, the fact that algae do not occupy arable land and can be cultivated in wastewater and marine environments is a particularly exciting feature. This differs from traditional bioethanol production, which relies on feedstocks derived from food crops, like sugar beets and corn (though non-edible feedstocks, like lignocellulose waste or crops, are emerging as viable alternatives). An added benefit: algae remove pollutants from wastewater during growth. Thus, the algae clean the water while the water provides a nutrient source for the algae to proliferate. The goal of the Ni Lab is to capitalize on these growth dynamics to engineer a system where the microbes double as wastewater-cleaning, fuel-producing machines.

“We propose, in the future, to use algae as a major pathway to treat wastewater,” Ni shared, in which case algae will be cultivated in wastewater to produce even more algae. “Then, [using] those algae as a [fuel] feedstock, we will produce a lot of biofuels, which will return back to society,” he continued. “Those algae are a renewable resource—that’s how this whole system will be working toward sustainability.” In other words, wastewater—which is never in short supply—provides a medium to support algae fermentation reactions, from which biofuel precursors can be extracted. The bioremediation features of the whole system are a bonus.

The team is also working on cultivating a circular bioeconomy in other ways, including engineering strategies to convert different biowaste (e.g., sewage sludge, food waste) into fuels.

Learn About a Career Using Microbes to Produce Biofuels

Beyond Fuel: Leveraging Waste to Produce High-Value Chemicals

Molten metal being poured into a casting mold at a steel mill.
Gas emissions from steel mills can turned into ethanol with the help of the gas-fermenting bacterium, Clostridium atuoethanogenum.
Source: iStock.com/simonkr.

Ni’s vision of chemically capitalizing on waste is applicable beyond the fuel realm. Indeed, fuels comprise only a subset of chemicals that are produced by human activities and can be found belching out of smokestacks, blanketing agricultural land or seeping into the ocean. With the help of microbes, scientists are finding ways to repurpose the often-problematic chemicals humans already make.

For instance, scientists demonstrated that the yeast Yarrowia lipolytica (known for its biotechnological potential) can convert hazardous waste from leather tanneries into amino-acid-rich supernatants, which can be repurposed as plant growth stimulants. There are also microbes that degrade and transform plastic into compounds that form the basis of products like nylon and biofuel. The options for microbe-driven waste conversion are vast and varied.

They also span all states of matter: liquid, solid—and gas. The biotechnology company LanzaTech leverages the gas-fermenting bacterium, Clostridium atuoethanogenum, to turn carbon-laden gas emissions from places like landfills or steel mills into ethanol, the chemical foundation for everything from fuel to perfume. The company’s technology involves “bolting on a brewery next to a steel mill,” explained Zara Summers, Ph.D., Chief Science Officer at LanzaTech, during a scientific session at ASM Microbe 2023. Gaseous waste is compressed, cleaned to remove toxins that could kill the bacteria and then fermented within a massive bioreactor (the “brewery”). The company can also “gasify” solid waste to feed into the system.

LanzaTech has 6 commercial plants with the capacity to produce 310,000 tons of ethanol from carbon emissions every year—preventing half a million tons of carbon from wafting into the atmosphere. “Humanity wants change for the climate, but [they] still buy stuff,” like fuel and clothes, Summers said. “We’re trying to let society live…but let people make a climate-smart choice.”

Researchers also recently engineered a strain of C. atuoethanogenum to produce isopropanol and acetate, 2 chemicals with applications in diverse industries, thus expanding the potential products and their capabilities. But the key word here? Engineered.

Got a Microbe, Want a Chemical? Call in the Metabolic Engineers

Most of the time, microbes are not inherently equipped to pump out chemicals at the efficiency and scale needed for industrial use, particularly if the goal is to “feed” them renewable carbon sources or waste material. Reaching that point requires engineering on the microscopic scale.

Diagram of metabolic engineering design process.Microbes can be engineered to produce chemicals of interest. Sometimes they already produce the chemical natively, other times genes from other microbes must be introduced. View larger image.
Source: ACS Publications.
Metabolic engineering involves “taking existing organisms and leveraging their metabolism in nature to enhance production of bioproducts,” explained Ying Zhang, Ph.D., an associate professor of cell and molecular biology at the University of Rhode Island. The practice, which involves altering existing genetic pathways in microbes, or introducing new ones, is central to the bio-based chemical enterprise nestled within the bioeconomy.

While metabolic engineering is a ubiquitous practice (most studies related to microbial chemical synthesis use it in some capacity), there are various approaches scientists can take. “Some organisms, by nature, already have the capacity to produce products that we desire, like ethanol,” Zhang said. In that case engineering efforts are focused on improving synthesis performance through tactics like overexpressing, downregulating or mutating endogenous genes. “But, in other cases, we take genes or enzymes we identify from elsewhere [e.g., other microbes], and introduce them into a new organism so that they gain the capacity to produce some useful products.”

This approach is required if the “new organism” has desirable characteristics for chemical synthesis (e.g., survives at high temperatures, grows rapidly, withstands toxins used during production), but doesn’t naturally produce the chemical of interest, or produces a precursor to the chemical but not the final product. Scientists then express genes from a single microbe that does manufacture the chemical, or engineer genes from multiple bacteria into a single biosynthetic pathway, in the host organism.

The engineering strategy researchers use ultimately depends on whether there are well-established engineering tools for the target organism, what physiological traits the microbe offers, whether those traits are conducive to chemical production and how much is known about the organism’s native metabolism.

Metabolic Engineering and Technology Go Hand-in-Hand

According to Zhang, the engineering approach a scientist takes also depends on uniting experimental data with computational power. Her lab builds genome-scale metabolic models—computational networks of all known metabolic pathways in an organism and how they interact—to inform engineering efforts. The models, which integrate diverse data (e.g., transcriptomics, metabolomics), serve as manipulatable blueprints, giving scientists a systematic view of a microbe. It allows them to delete or modify genes to determine how mutations might impact chemical output—all without touching a pipette.

With a model in hand, “our collaborators, who are geneticists or biochemists, don't need a search in the dark and randomly change things to see what works,” Zhang said. “Rather, they have a more guided approach where we say, 'Okay, out of the 100 targets, maybe 10 of them will be optimal targets and you should try [them] first.'”

Colored SEM image of P. furiosus cells. The hyperthermophilic archaeon, Pyrococcus furiosus, has been engineered to produce a range of chemicals.
Source: Wikimedia Commons.
Zhang and her colleagues have demonstrated the value of this modeling-first approach for biofuel production. The team generated the first metabolic model of the hyperthermophilic archaeon Pyrococcus furiosus, an organism engineered to produce different fuels and chemicals, including ethanol. Previous research yielded a strain of P. furiosus that makes ethanol at 95° C—a valuable characteristic, as high-temperature fermentation can prevent contamination during production—but it does so inefficiently. Zhang’s team wanted to fix that. They tested a panel of different mutations with their model to determine which combination (and simulated culture conditions) yielded the best benefit in ethanol production. “We found a bunch of mutants that could be useful for further testing, and some are now being examined in the lab,” Zhang shared. “We’re excited to see the next steps.” The study highlights how technology begets strategic experimental action.

With that, the more scientists understand about the biosynthetic pathways of microbes, the greater the potential to harness and/or manipulate those pathways to produce valuable chemical products. Gaining such knowledge leans heavily on the growing spate of technological and analytical tools (e.g., omics, machine learning, modeling) that allow researchers to tease apart the intricacies of microbial life. Using these tools to profile microbial communities and/or metagenomic content in diverse environments—from swamps to hydrothermal vents—can also expand the repertoire of organisms scientists use to make chemicals and diversify the chemicals they make.

Most of the research in this article was published in ASM Journals! Do you have cutting-edge work to share? Submit your manuscript now.

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We're All in This Together

The widespread implementation of microbial-produced or derived chemicals, particularly those involving the metabolic breakdown and conversion of waste, is still in its infancy. Cost is a primary limitation. While there are long-term economic benefits to investing in biofuels and biochemicals, non-renewable resources (fossil fuels) and existing production processes cost less in the short-term. This has limited the commercial expansion of renewable fuels and chemicals. Facilitating such expansion requires buy-in from government and industry partners, something that is happening at the level of individual companies and projects.

For example, LanzaTech, which is already operating in the commercial space, received a $200 million award from the U.S. Department of Energy (DOE) in March 2024 for a new project with their partner, Technip Energies, to produce sustainable ethylene (an ethanol-derived building block for chemicals and materials). Ni is working with various industry partners to scale up his team’s algae-wastewater-biofuel system, and it’s looking “very promising.” Moreover, the DOE awarded $118 million in 2023 to various projects to accelerate domestic biofuel production.

The path forward is ultimately a multidisciplinary one, pulling scientists and stakeholders from a network of disciplines and industries. Zhang emphasized that her research would be impossible without the foundational work done by other scientists, and that bringing microbially generated chemicals to market requires collaboration. “We all bring in very different expertise and perspectives,” she said. “I don't think a single person or lab can pull off all aspects involved in this.” From Zhang’s perspective, we must approach the future of the biochemical economy like we are all in it together—because we are.

Heading to ASM Microbe 2024? Check out this curated itinerary of sessions on the bioeconomy, including those discussing the use of algae for bioproduction and synthetic biology for natural product discovery.

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Author: Madeline Barron, Ph.D.

Madeline Barron, Ph.D.
Madeline Barron, Ph.D., is the Science Communications Specialist at ASM. She obtained her Ph.D. from the University of Michigan in the Department of Microbiology and Immunology.

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