September 26

New Model Accelerates Engineering of Microbes for Biomanufacturing

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BioP2P Staff

Scientists at Lawrence Berkeley National Laboratory said they have created a workflow for developing new microbial strains that makes it quicker, easier, and less expensive than existing methods.

A team led by senior scientist Aindrila Mukhopadhyay has developed a workflow that combines CRISPR gene editing with a suite of computational models of microbial gene expression and enzyme activity that can be used to predict the necessary gene edits. Their latest work was recently published in the journal Cell Reports.

They said under the approach they can design a bacterium that can make target molecules by converting a type of plant tissue that often goes to waste in agriculture and forest management. The approach will help make the biomanufacturing industry more sustainable.

“Much of strain design is still trial-and-error based, which is laborious and time consuming. We’ve demonstrated that pairing targeted approaches that focus on specific genes and proteins with methods that model the entire genome, you can tremendously reduce product development cycles from years to months,” said co-first author Thomas Eng, Deputy Director of Host Engineering at the Joint BioEnergy Institute, a Department of Energy Bioenergy Research Center led by Berkeley Lab’s Biosciences Area.

The workflow, called Product Substrate Pairing (PSP), has already shown great promise for engineering strains that can convert common bacterial food sources into target molecules. But to demonstrate the true power of the approach, their new work concentrated on developing a strain that could feed on molecules derived from lignin – a type of tough, fibrous plant tissue. Lignin is an ideal eco-friendly precursor to feed biomanufacturing microbes because it is abundant in the hundreds of millions of tons of plant waste that is generated each year from post-harvest crops and landscape clearing.

Currently, most biomanufacturing processes rely on simple sugar molecules derived from specially grown crops called feedstocks, but by upcycling the copious lignin already available, JBEI scientists hope to make bio-based manufacturing more renewable and carbon-neutral.

“The whole enterprise of sustainable biomanufacturing hinges on our ability to use a wide range of starting materials,” said Mukhopadhyay, who is the Vice President for Biofuels and Bioproducts, and Director of Host Engineering at JBEI. “However, individual methods can be limited by our incomplete knowledge of less understood precursors. Our ensemble workflow uses well-developed tools and should be applicable to many carbon sources, microbial systems, and biomanufacturing targets.”

You can read the full release on the LBL website

 

 


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