Researchers from the Joint BioEnergy Institute (JBEI), led by Aindrila Mukhopadhyay, who is a senior scientist and Science Deputy for Biosciences’ Biological Systems and Engineering (BSE) Division as well as the Vice President for Biofuels and Bioproducts, and Director of Host Engineering at JBEI, have developed a new framework that reduces the time of developing new bioproducts. 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. However, each biomanufactured product on the market today is the investment of years of work and many millions of dollars in research and development funding.
“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 JBEI.
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. This new workflow, called Product Substrate Pairing (PSP), has already shown great promise for engineering strains that can convert common bacterial food sources into target molecules.
The research team also demonstrated 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 special sauce comes from how well-established tools are integrated together to make a workflow that is applicable to any microbe and any bioprocess,” said co-first author Deepanwita Banerjee, who is a computational research scientist in JBEI’s Host Engineering Group. “Our paradigm-shifting paper demonstrates a logical and efficient way of building and testing strains that is grounded in how the cells are behaving at every step of the development cycle. This is a big step toward a predictive understanding of cellular function.”
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