Exploring the frontier of metabolic pathway engineering to combat climate change
Imagine an invisible world teeming with trillions of microscopic life forms that silently dictate the fate of Earth's climate. Every day, in soil, lakes, and oceans, countless microorganisms engage in a biochemical tug-of-war over carbon—either storing it safely or releasing it into the atmosphere as carbon dioxide. This microscopic drama has macroscopic consequences, influencing global temperatures, ecosystem health, and our climate future.
At the heart of this battle lies a fascinating scientific frontier: metabolic pathway rewiring. Scientists are learning to reprogram how microbes process carbon, potentially turning them from carbon emitters into carbon storage allies. By understanding and engineering the very biochemical machinery that determines carbon's fate, researchers are developing innovative strategies to reduce carbon loss and transform our approach to climate change mitigation.
Carbon forms the fundamental backbone of life on Earth, cycling continuously between the atmosphere, oceans, land, and living organisms. This natural cycle has maintained equilibrium for millennia, but human activities have dramatically disrupted this balance, releasing historic amounts of carbon dioxide into the atmosphere and accelerating climate change.
Microbes play an overlooked yet critical role in this cycle. When microbes break down plant matter, the carbon follows one of two paths: it either builds microbial bodies (storage) or is respired as CO₂ into the atmosphere (loss) 1 . Understanding this microbial decision-making process is crucial for addressing climate change.
Carbon is used to build DNA, proteins, and other cellular components, keeping it sequestered in biological matter 1 .
Microbial biomass acts as a temporary carbon sink
Carbon is channeled through metabolic processes that release it as CO₂, primarily through the tricarboxylic acid (TCA) cycle 1 .
In 2024, a Northwestern University-led research team made a critical breakthrough in understanding microbial carbon processing. For the first time, they precisely tracked how different plant compounds move through bacterial metabolism and contribute to atmospheric CO₂ 1 .
The researchers designed an elegant experiment using the common soil bacterium Pseudomonas putida. Instead of studying individual compounds as previous researchers had done, the team used a mixture of plant derivatives representing what bacteria encounter in nature. To follow the carbon's journey, they employed isotope labeling, which allowed them to track specific carbon atoms from each compound type inside the cell 1 .
Common soil bacterium used in the groundbreaking carbon tracking experiment 1 .
Researchers prepared a mixture of plant derivatives representing structural components of plants—specifically lignin carbons (non-sugar aromatic units) and cellulose carbons (glucose sugar units) 1 .
Individual carbon atoms were tagged with isotope labels, functioning as microscopic tracking devices that would reveal their metabolic pathways 1 .
The labeled plant matter was introduced to Pseudomonas putida bacteria, and researchers monitored the routes the different carbon types took through the bacterial metabolism 1 .
Using quantitative analysis, the team measured how much CO₂ was produced from each type of plant carbon 1 .
The researchers examined data from previous experiments on other soil bacteria to determine if their findings applied more broadly across microbial species 1 .
The findings revealed a striking imbalance in how different plant compounds contribute to carbon loss:
| Plant Compound Type | Metabolic Pathway | CO₂ Production Relative to Cellulose |
|---|---|---|
| Cellulose carbons (glucose sugar units) | Glycolytic and pentose-phosphate pathways | 1x (baseline) |
| Lignin carbons (non-sugar aromatic units) | Tricarboxylic acid (TCA) cycle | 3x |
The data revealed that "microbes respire three times as much CO₂ from lignin carbons compared to cellulose carbons" 1 . Even when microbes consumed these carbons simultaneously, their metabolic processing resulted in disproportionate CO₂ emissions based on the chemical structure of the carbon source.
This discovery helps explain why some organic matter contributes more significantly to atmospheric CO₂ than others, and it provides crucial information for predicting how carbon in soil will affect climate change as temperatures rise and different types of organic matter become available to microbes.
The story of microbial carbon management extends far beyond soil. Recent research on lakes reveals how human activities are dramatically altering microbial carbon processing in aquatic ecosystems 2 .
A comprehensive 2025 study examined 14 lakes spanning a 3,369 km gradient along China's Yangtze River and its front basin. These lakes were surrounded by varying degrees of land-use conversion, from pristine natural landscapes to areas heavily modified for agriculture and urban development 2 .
The research uncovered a clear and concerning pattern: when natural lands were converted to anthropogenic uses (farmland and built areas) at rates exceeding 30%, the result was substantial carbon loss in adjacent lakes—greater than 50% 2 .
This dramatic carbon loss was driven by a chain reaction: land conversion increased nutrient inputs into lakes, which stimulated microbial carbon utilization. The elevated nutrients caused a fundamental shift in microbial communities, with nutrient-sensitive species being replaced by nutrient-preferential species 2 .
| Nutrient-Sensitive Species (Decreasing) | Nutrient-Preferential Species (Increasing) | Resulting Change in Carbon Utilization |
|---|---|---|
| Roseomonas | Desertimonas | Enhanced utilization of itaconic acid, phenylethyl-amine, and glycerol |
| Methylocystis | Clostridium sensu stricto |
These new microbial communities showed distinct preferences for specific carbon substrates, enhancing the utilization of compounds like itaconic acid, phenylethyl-amine, and glycerol, thereby accelerating carbon loss from these ecosystems 2 . The study demonstrated that microbes in water were more responsive to these environmental changes than those in sediment 2 .
>30% land conversion leads to >50% carbon loss in lakes 2
Armed with knowledge of how microbes naturally process carbon, scientists are now developing sophisticated methods to rewire their metabolic pathways. This emerging field of metabolic engineering uses genetic engineering techniques to modify metabolic pathways within cells, increasing the yield of desired products while reducing waste and carbon loss 5 .
At its core, metabolic engineering focuses on optimizing Central Carbon Metabolism (CCM)—the most fundamental metabolic process in living organisms that includes glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway 5 . By modifying this fundamental machinery, scientists can redirect carbon flow away from CO₂-producing pathways and toward product synthesis or carbon storage.
| Strategy | Mechanism | Application Examples |
|---|---|---|
| Introducing heterologous pathways | Adding new metabolic routes not naturally present in the organism | PHK pathway conversion of fructose-6-phosphate to acetyl-CoA without CO₂ production 5 |
| Modular deregulation | Systematically removing natural regulatory mechanisms in metabolic modules | 4.7-fold increase in 3-HP productivity from xylose in engineered yeast |
| Carbon source co-utilization | Enabling simultaneous use of multiple carbon sources to improve efficiency | Co-feeding of glucose with xylose, glycerol or C1 compounds 4 |
| Enzyme optimization | Replacing or modifying key enzymes to alter metabolic flux | Using mutant enzymes that favor carbon retention over loss |
One particularly effective approach involves introducing the phosphoketolase phosphotransacetylase (PHK) pathway into microorganisms. This simple two-enzyme pathway facilitates direct synthesis of acetyl-CoA (a key metabolic intermediate) while avoiding CO₂-producing steps 5 . When implemented in yeast, this pathway has been shown to increase production of valuable compounds like fatty acids and aromatic molecules while reducing carbon loss 5 .
Recent advances have demonstrated the power of modular approaches that treat central carbon metabolism as interconnected modules that can be independently optimized. In one groundbreaking study, scientists employed five different engineering strategies—including promoter engineering, transcription factor manipulation, and biosensor construction—to deregulate carbon metabolism in yeast . This systematic approach achieved a remarkable 4.7-fold increase in productivity of 3-hydroxypropionic acid from xylose, a non-glucose carbon source .
Increase in 3-HP productivity from xylose in engineered yeast using modular deregulation
Carbon atoms tagged with stable isotopes allow researchers to trace metabolic pathways with precision 1 .
Specialized assay plates containing 31 different carbon sources for profiling microbial communities 2 .
Reagents for 16S rRNA gene amplicon sequencing to identify microbial species 2 .
Advanced instruments like the LiCellMo system for real-time metabolic monitoring 3 .
As metabolic engineering advances, scientists are exploring increasingly sophisticated approaches to carbon management. One exciting frontier involves engineering microorganisms to utilize one-carbon (C1) compounds like carbon dioxide, methane, and methanol as feedstocks 6 8 .
Future efforts will likely focus on pairing C1 substrates with complementary energy sources, including light-harvesting systems and electrochemical approaches that can provide the necessary energy input without creating additional carbon emissions 6 8 .
The rewiring of endogenous metabolic pathways represents a paradigm shift in our relationship with carbon—from viewing it as a waste product to valuing it as a renewable resource. By understanding and optimizing how microbes process carbon at the most fundamental biochemical level, scientists are developing tools to reduce carbon loss across diverse ecosystems and industrial processes.
As research advances, these approaches may transform agriculture, waste management, and manufacturing, creating a more circular carbon economy where carbon is continuously recycled rather than released into the atmosphere. The invisible world of microbial metabolism, once understood and thoughtfully directed, offers powerful solutions to one of humanity's greatest challenges—managing Earth's carbon cycle to maintain a stable climate for future generations.
The journey to rewire metabolism for reduced carbon loss is just beginning, but it already reveals a promising truth: some of our most powerful allies in addressing climate change may be the microscopic organisms that have been processing carbon since life began.