The Inscripta Blog

May 25, 2021

Inscripta Helping to Flip the Script to Combat Climate Change

Many would agree that we are at a crisis point when it comes to climate change. It is becoming clear that the historical, fossil-fuel based models of carbon, energy and material cycling through the economy are incompatible with maintaining a sustainable global environment.

What role could biotechnology play to reduce carbon emissions, adapt to new climate conditions, and address the needs of the 21st century and beyond?

A crucial one, according to a report recently released by BIO. It showcases Inscripta as an example of a company ‘flipping the script’ of exclusive CRISPR gene editing by launching a benchtop platform that can perform thousands of gene edits at the push of a button.

As the “Biotech Solutions For Climate” report notes, the first step to affecting change is shifting our reliance on petroleum and other non-renewable resources to renewable biomass. But this depends on the availability of sustainable biomass feedstocks. Not only do we need sustainable ways to produce usable biostock by improving yields on existing crops and low-input production systems, but also finding ways to use biomass that would otherwise be wasted.

A common problem with abundant raw feedstocks like switchgrass or lignocellulose is that they require extensive pretreatment to release fermentable carbon sources, and the pretreatment chemicals are difficult to separate downstream. Lignocellulosic biomass also contains toxic compounds that inhibit the growth of microbial strains.

Scientists have been able to identify resistance pathways and mechanisms of toxic compound inhibition, but there is still a great need to overcome these challenges to enable full “cell factory scale-up” at production level.

As Inscripta data scientist Stephen Federowicz demonstrates in this video, we were able to recapitulate decades of work on improving tolerance in just a few months using the Onyx™ Digital Genome Engineering benchtop platform.

After libraries of E. coli cells were engineered on the Onyx with a total of around 25,000 knock-out and promoter edits, they were pooled into cultivation flasks and subjected to different conditions to test their tolerance to pH, salt and biomass inhibitors such as furfural.

NGS barcode sequencing and analysis identified around 3,800 edits that were enriched or depleted among the genome-wide knockout and promoter ladder variants. Previously validated genes for furfural response were confirmed as hits, but there were also nearly 3,700 other edits across the genome that seemed to confer resistance to furfural.

“So, if you’re a strain engineer and you’re trying to rapidly determine all of the genetic changes that can get you to an optimal production level, with optimal scale properties, a simple study like this can elucidate hundreds of targets for you to work off of,” Federowicz said.

Further analysis of the genes identified clusters where knockouts were more beneficial in conferring tolerance, and clusters where promoters did the trick. Some genes seemed to be sensitive to either approach, while others were insensitive to any of the changes.

Hundreds of genes fell into these coordinated modules, which could be used to select gene targets with predictable responses. This could help drive forward engineering experiments in which you select the most promising edits and recombine them to get even more tolerant and productive strains.

This work demonstrated that even for very well-studied inhibitory compounds, there are huge numbers of additional genomic targets that could be exploited to increase strain tolerance. This is just one example of how the Onyx platform can be used to address climate change and advance the emerging bioeconomy.

Additional work is also being undertaken by some of our earliest users. The technology used in the Onyx platform has enabled researchers at Willow Biosciences to create a synthetic cannabinoid with a small physical, financial, and environmental footprint. And our first commercial shipment went to GeneMill, an open access synthetic biology foundry at the University of Liverpool with a passion for promoting sustainable science.

We look forward to seeing all the ways our technology is applied to flip the script in climate change.