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Metabolic engineering allows robust, standardized fermentation that is predictive at scale

By Scott Jenkins |

Production of bio-based chemicals has important environmental, cost and functional benefits, but historical approaches have lacked robustness to the commercial process environment and have proven costly to develop. A platform technology developed by DMC Biotechnologies (Boulder, Colo.; www.dmcbio.com) was designed to standardize microbial fermentation, provide high-throughput approaches that predictably scale to commercial volumes, and to create biocatalysts that are robust under industrial process conditions.

DMC’s patented technology, known as Dynamic Metabolic Control, effectively decouples the microbes’ growth phase from production of the desired molecule in the fermentation vessel. “When the biocatalysts are grown, they are not producing any product,” explains Matt Lipscomb, CEO of DMC Bio. “Once the desired biocatalyst concentration is reached, the microbes stop growing and begin producing a desired product.”

This transition is achieved by genetically engineering the microbes’ metabolic pathways with targeted proteolysis, gene silencing and other tools, such that an environmental trigger will change the expression of certain genes, shutting down those genetic elements that enable growth and expressing others that are responsible for making the product. “We grow the engineered microbes using a limiting macronutrient that, when depleted, triggers gene-expression changes that turn on the production pathway,” Lipscomb says.

Re-writing the microbial genetics associated with growth and production allows the microbes to perform well under a broader range of process conditions, Lipscomb says, so “we don’t have to do extensive process development at each scale.” The fermentation is standardized in terms of feed, growth media and other parameters to optimize production.

The company is currently operating a pilot-scale process for producing specialty amino acids for the animal feed and human supplement markets, and plans to use its metabolic control technology to scale up fermentation processes for other products, such as organic esters for the personal care market, and terpenoids for the flavor and fragrances market.

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