Using engineered microbes as microscopic factories has given the world steady sources of life-saving drugs, revolutionized the food industry, and allowed us to make sustainable versions of valuable chemicals previously made from petroleum.
But behind each biomanufactured product on the market today is the investment of years of work and many millions of dollars in research and development funding. Berkeley Lab scientists want to help the burgeoning industry reach new heights by accelerating and streamlining the process of engineering microbes to produce important compounds with commercial-ready efficiency.
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 Cell Reports.
“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, who is the Deputy Director of Host Engineering at the Joint BioEnergy Institute (JBEI), 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.