March 30, 2015
Cleaner Living Through Smarter Microbiology
Petroleum-derived products undergo a complicated, energy intensive journey from the oil deposits deep underground to our homes, cars, and clothing. “Our lifestyle is very difficult on the environment,” explains Emily Leproust, CEO of Twist Bioscience. “It’s expensive and it’s harmful; there needs to be another way.”
Fortunately, it seems that there may in fact be an alternative, derived from the strategic manipulation of microbial metabolic pathways. Many organisms process sugars into various carbon-bearing compounds, and enzymatic reactions can be re-ordered to produce different compounds of interest – nylon, for example, rather than ethanol, from engineered autotrophic fermenters. “That way,” explains Leproust, “the carbon in the carpet you buy comes from the atmosphere, and air is free.”
At least, that’s the hope. Bioengineers predict that just half a percent of a yeast organism’s genome, or less, would need to be altered to rework carbon intermediates into useful chemicals. The two most promising approaches involve directed evolution, in which the adaptive playing field is tilted in favor of a desired outcome, and design, a computational approach in which biologists use enzyme mechanistic details to predict optimized modes of reactions. Both are difficult strategies that require a lot of fundamental research, but if this rosy view of the bio-industrial future is realized, a drastic lifestyle change may be obviated by technological progress. “We will still use all of the chemicals we use today,” predicts Leproust, “but they will be made by fermentation of sugar or cellulose in yeast.”
Such advances will be facilitated in large part by DNA synthesis technology: mixing and matching genetic elements requires custom-made sequences, which Twist provides in partnership with its clients. “Customers want to try one or ten or 100 genes,” says Leproust, “to fully test the options and see what’s best.” This approach effectively short-circuits evolution, drastically broadening the search space of biological capability.
Leproust also sees agriculture as an important sector in a future beset by unpredictable climate and food security challenges. She calculates that the planet will need 60% more food in the coming three decades to feed the human population, an equation that runs up against land scarcity and enormous energetic requirements for fertilizer production. Potential solutions include enhanced plants that can handle drought or variable water conditions, as well as bacterial symbionts engineered to fix nitrogen and live among the roots of wheat, rice, or corn plants. “It’s a huge evolution in thinking,” Leproust notes; “ten years ago, bacteria were thought to be the enemy.”
For Twist, the key to making customized DNA sequences to achieve these important bioengineering aims was scalability. 96-well plates, in which distinct chains are produced in half-mililiter compartments, was state-of-the-art technology in the mid-1990s, and the practice continued largely because mechanized instruments were built to accommodate such plates. With 96 different oligonucleotide chains, each plate could produce approximately one gene.
“We thought, ‘let’s shrink it, optimize the chemistry,’” recalls Leproust, “and to do that, we developed silicon-based technology.” The resulting DNA-synthesis platform reduced the volume from dozens of microliters to hundreds of nanoliters, minimizing the amount of required reagents and thereby lowering the overall cost. Silicon is also a better conductor of heat than the previous plastic-based approach, which allowed the chain-elongating reactions to happen faster. What’s more, the approach is “agnostic to chemistry,” as Leproust puts it, meaning Twist can just as easily product RNA, or exotic nucleotide chains with synthetic bases.
*This article is part of a special series on DNA synthesis that also appears on Wired.com