Researchers publishing in ACS Sustainable Chemistry & Engineering have rewired one such microorganism to help combat greenhouse gases in the environment. It absorbs CO2 gas and makes mevalonate, an important building component for drugs.
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Certain microbes can make humans sick or destroy food, but others are necessary for living. These microorganisms can also be designed to produce particular molecules.
The growing concentration of greenhouse gases in the atmosphere has caused widespread global warming. To begin addressing the issue, greenhouse gas emissions, especially CO2, must be drastically decreased.
Methods for capturing CO2 are being developed, and one intriguing one involves bacteria. Genetic engineering can alter the microorganisms' native metabolic pathways, transforming them into miniature living factories capable of producing various products, including insulin.
Cupriavidus necator H16, a bacterium regarded for its generally unfussy feeding habits, is one possible microbial factory. Since it can survive on only CO2 and hydrogen, the bacterium is an excellent option for absorbing and converting gases into larger molecules. However, while the microbe’s DNA can be rewired to make novel proteins, it is not particularly good at remembering those new instructions over time.
To put it scientifically, the plasmids (genetic instructions) are unstable. Katalin Kovacs and colleagues sought to investigate whether they might increase C. necator’s capacity to recall new instructions while also producing important carbon-based building blocks from CO2 gas.
The researchers bgan manipulating C. necator’s metabolic processes, which transform CO2 into larger six-carbon molecules. The key to enhancing the plasmid's stability is RubisCo, an enzyme that allows the bacterium to use CO2.
Essentially, the new plasmid was associated with the enzyme, so if a cell did not remember the new instructions, it would be unable to produce RubisCo and would die. Meanwhile, the surviving cells with higher memory would survive and reproduce, spreading the plasmid.
In experiments, the newly modified microbes produced substantially more mevalonate, a six-carbon molecule, than a control strain. Mevalonate is a molecular building block for a wide range of substances in both living and synthetic systems, including cholesterol and other steroid molecules with therapeutic potential.
This study used bacteria to synthesize the most mevalonate from CO2 or other single-carbon reactants. According to the researchers, this is a more cost-effective carbon fixation system than prior systems incorporating C. necator, and it might be expanded to include other microbial strains.
The Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council of the United Kingdom provided funding, which the authors acknowledge.
Journal Reference:
Garavaglia, M., et. al. (2024) Stable Platform for Mevalonate Bioproduction from CO2. ACS Sustainable Chemistry & Engineering. doi.org/10.1021/acssuschemeng.4c03561