Tiny microbes can yield huge benefits for green biomanufacturing

May 08, 2023

(Nanowerk News) A research team led by Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley have engineered bacteria to introduce novel carbon products to nature that could provide a powerful route to sustainable biochemistry.

Progress – which was recently announced in the journal Natural (“Complete integration of carbene transfer chemistry into biosynthesis”) – uses bacteria to combine natural enzymatic reactions with new-to-nature reactions called “carbene transfer reactions”. This work could also one day help reduce industrial emissions because it offers a sustainable alternative to chemical manufacturing processes that typically rely on fossil fuels. During experiments at DOE’s Joint BioEnergy Institute, researchers observed strains of the Streptomyces bacteria engineered to produce cyclopropane, a high-energy molecule that has the potential to be used in the sustainable production of new bioactive compounds and advanced biofuels. (Image: Jing Huang)

“What we demonstrated in this paper is that we can synthesize everything in this reaction – from natural enzymes to carbenes – in bacterial cells. All you need to add is sugar and the cells do the rest,” said Jay Keasling, principal investigator of the study and CEO of the Department of Energy’s Joint BioEnergy Institute (JBEI).

Carbene is a highly reactive carbon-based chemical that can be used in many types of reactions. For decades, scientists have wanted to use the carbene reaction in the manufacture of fuels and chemicals, as well as in drug discovery and synthesis.

But this carbene process can only be carried out in small amounts in a test tube and requires expensive chemicals to drive the reaction.

In the new study, researchers replaced expensive chemical reactants with natural products that can be produced by engineered strains of the Streptomyces bacteria. Because bacteria use sugars to produce chemical products through cellular metabolism, “this work allows us to carry out carbene chemistry without the toxic solvents or toxic gases normally used in chemical synthesis,” said first author Jing Huang, a Berkeley Lab postdoctoral researcher at Keasling Laboratory. “This biological process is much more environmentally friendly than the current way of chemical synthesis,” said Huang.

During the experiments at JBEI, the researchers observed engineered bacteria metabolizing and converting sugars into carbene precursors and alkene substrates. The bacteria also express an evolved P450 enzyme that uses the chemical to produce cyclopropane, a high-energy molecule that has the potential to be used in the sustainable production of new bioactive compounds and advanced biofuels. “We can now carry out this exciting reaction inside a bacterial cell. The cells produce all the reagents and cofactors, which means that you can scale these reactions to a very large scale” for mass manufacturing, said Keasling.

Recruiting bacteria to synthesize chemicals could also play an integral role in reducing carbon emissions, said Huang. According to other Berkeley Lab researchers, nearly 50% of greenhouse gas emissions come from the production of chemicals, iron and steel, and cement. Limiting global warming to 1.5 degrees Celsius above pre-industrial levels will require halving greenhouse gas emissions by 2030, says a recent report by the Intergovernmental Panel on Climate Change.

Huang said that while this fully integrated system is conceivable for a large number of carbene donor molecules and alkene substrates, it is not yet ready for commercialization.

“For every new advancement, someone needs to take the first step. And in science, it can take years before you succeed. But you have to keep trying – we can’t give up. I hope our work will inspire others to continue to seek greener and more sustainable biomanufacturing solutions,” said Huang.

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