Greener Synthetic Pathways Award: Life Technologies

Life Technologies received the Greener Synthetic Pathways Award for developing less wasteful methods to make reagents used in molecular biology techniques, such as the polymerase chain reaction (PCR), which is widely used to replicate pieces of DNA to generate thousands to millions of copies. DNA amplification is often needed to carry out testing for basic research, genetic engineering, forensic investigations, infectious disease identification, food safety, and personalized medicine.

Manufacturing some of the complex reagents used in PCR such as deoxyribonucleotide triphosphates (dNTPs) generally produces thousands of times as much waste as product. Life Technologies scientists came up with a more efficient process for making these individual building blocks used to replicate the DNA.

Conventional syntheses of high-purity dNTPs involve multiple steps that require isolation and purification of intermediates and use excessive volumes of toxic or hazardous solvents and reagents, including zinc chloride, triphenylphosphine, dipyridyldisulfide, dimethylformamide, and dichloromethane. “Our research team saw an opportunity to improve sustainability within the day-to-day processes in our facility,” says Anil Kore, Life Technologies’ senior manager for manufacturing.

Kore and his colleagues developed a streamlined three-step, one-pot method to synthesize dNTPs that eliminates the need to transfer reaction mixtures and for protection-deprotection steps, thereby reducing the number and amount of reagents and solvents required. “By using these new dNTP routes,” Kore says, “worker exposure to hazardous material is minimized and waste production is significantly reduced—improving safety and our impact on the environment.”

In 2011, Life Technologies implemented the greener synthetic routes for full-scale production of dNTPs at its Austin, Texas, manufacturing site. According to the company, organic solvent consumption has been reduced by up to 95% and other hazardous waste up to 65%, eliminating 1.5 million lb of hazardous waste per year.

“Life Technologies’ improvements to PCR are remarkable,” comments chemistry professor Bruce H. Lipshutz of the University of California, Santa Barbara, a 2011 Presidential Green Chemistry Challenge Award winner. “The method as originally described and practiced today leads to an enormous amount of waste relative to product—in terms of the Sheldon E factor [kilograms of waste per kilograms of product], values that are off the charts. The newly disclosed one-pot process, in the spirit of green chemistry, avoids pollution in the form of millions of pounds of not just waste, but notably, hazardous waste.”