Engineering new lipases for nutritional applications

点击翻译按钮获取中文摘要

Over the past decade, scientific research has reported on numerous health benefits associated with increased intake of omega-3-enriched oils. Because these oils are often insufficient in the diet, the global demand for high quality supplements fuels a multi-billion $/yr industry, and is booming. The majority of the world supply is extracted from fish oils, yet current extraction processes suffer from low recovery. As a result, supplements are only moderately enriched in the beneficial omega-3 oils, which means larger doses must be taken. In particular, the recovery of omega-3 oils is crippled by poorly selective catalysts and lengthy reaction times. In this concerted research effort, the enzyme evolution laboratory of Joelle Pelletier will guide the engineering of better biocatalysts for production of omega-3-enriched oils at DSM Nutritional Products Canada. Biocatalysts, or enzymes, provide a consumer-safe and environmentally sound approach to industrial enrichment of omega-3 oils. DSM processes millions of kg of fish oil per year using naturally-occurring enzymes from the lipase class. Despite lengthy attempts to identify lipases with better properties, their omega-3 enrichment ratio stands capped at 60%. With the goal of increasing the omega-3 content to 70-80%, we have collaboratively developed a platform to engineer the desired properties into the enzyme (supported by an Engage grant, April-Oct 2015). We genetically modified a lipase enzyme using computational guidance, and established a protocol to screen for improved omega-3 enrichment in a high-throughput format, using robotic automation to query specific features. We are currently poised to scale up this effort, to produce hundreds of improved variants for more rigorous testing. We will take the variant with the most suitable properties (including expression, stability, pH profile) forward for scale-up and optimization of reaction conditions at DSM. This project will yield an improved biocatalyst for commercial use, better access to high quality nutritional supplements, and a unique training opportunity in applied biocatalyst engineering.