Mobilizing the Planet’s Genetic Diversity with Synthetic Biology
1,4-Butanediol isn’t exactly the flashiest product on the market: with a four-carbon chain bounded by alcohol groups, the thick, colorless liquid is one of those “industrial chemicals” that makes the eyes glaze over. But the diminutive molecule is worth some serious cash, with an estimated global market cap of $2 billion. Ultimately, 1,4-butanediol, also known as BDO, facilitates the production of a range of plastics, polyurethanes, and elastic fibers, making everything from skateboards to Spandex possible.
In a story that is increasingly pervasive in the field of molecular synthesis, BDO’s chemical production protocol – typically involving toxic reactants like formaldehyde – is being challenged by a biological approach. Several years ago, Genomatica secured a patent for “a non-naturally occurring microbial organism” that contains five exogenous genes “expressed in sufficient amounts to produce 1,4-BDO”.
To Axel Trefzer, a Director of R&D in ThermoFisher’s Synthetic Biology unit, U.S. patent number 8067214 represented an important step for an evolving field, a step that was made possible through gene synthesis technologies. To design their BDO production pathway, Genomatica researchers looked for enzymes that could accomplish each reaction and placed them together into a stable host microorganism. With control over the sequences being used, the whole process took just a few years.
This rapid march to market was not the norm for an industry dominated by corporate behemoths. A decade earlier, in the late 1990s, DuPont engineered a microbe to produce a similar chemical, 1,3-propanediol. But it took more than a decade, according to Trefzer’s estimate, “because they worked a lot more with natural sequences, strain optimization, and much more trial and error.” With a design perspective enabled by gene synthesis, however, Genomatica “was much faster in the process from idea to commercially viable product,” notes Trefzer.
Cases like BDO production demonstrate the fact that a wide range of the planet’s genetic diversity is newly accessible in the service of biomolecule synthesis. In the past, only genes from well-understood, culturable organisms could be manipulated, and even then the process was cumbersome. But as DNA sequencing and synthesis technologies have advanced, “a lot of the sequences people use in these synthetic biology projects,” says Trefzer, “come from difficult-to-cultivate organisms or from metagenomic sequences” that are pulled out of a more complicated microbial mixture.
Despite its growing track record, DNA synthesis is still an emerging field, and ThermoFisher is eager to grow the community of users, realizing that a rising tide lifts all boats. “There is still a significant group of the market that is just discovering the abilities you have with synthetic DNA,” says Trefzer, “and we understand that there’s a whole range of customers on the spectrum, migrating away from classical approaches.” To ease the transition, the company created the first online portal for gene ordering, a functionality that has now been widely adopted. Upon receipt, the sequence is run through biosafety and biosecurity checks, and ultimately constructed through the enzymatic assembly of shorter oligonucleotide chains.
This unparalleled freedom has created a new sense of biological possibility. “Modifying a physical template by PCR or mutagenesis only allows you to make a limited number of changes,” Trefzer explains, “but de novo writing of biological information has completely opened up how far you can think, and how far you can go.”
*This article is part of a special series on DNA synthesis that also appears on Wired.com
To hear more from Axel Trefzer and other great thought leaders, check out SynBioBeta’s London event this April. For more information, click here!
Jeffrey Marlow is an author on WIRED