By linking the cell’s survival to the production of their target compound, the team was able to trick the microbe into creating xanthommatin. To do this, they started with a genetically engineered “sick” cell, one that could only survive if it produced both the desired pigment, along with a second chemical called formic acid. For every molecule of pigment generated, the cell also produced one molecule of formic acid. The formic acid, in turn, provides fuel for the cell’s growth, creating a self-sustaining loop that drives pigment production.

“We made it such that activity through this pathway, of making the compound of interest, is absolutely essential for life. If the organism doesn't make xanthommatin, it won't grow,” said Bushin.

To further enhance the cells’ ability to produce the pigment, the team used robots to evolve and optimize the engineered microbes through two high-throughput adaptive laboratory evolution campaigns, which were developed by the lab of study co-author Adam Feist, professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering and senior scientist at the Novo Nordisk Foundation Center for Biosustainability. The team also applied custom bioinformatics tools from the Feist Lab to identify key genetic mutations that boosted efficiency and enabled the bacteria to make the pigment directly from a single nutrient source.

“This project gives a glimpse into a future where biology enables the sustainable production of valuable compounds and materials through advanced automation, data integration and computationally driven design,” said Feist. “Here, we show how we can accelerate innovation in biomanufacturing by bringing together engineers, biologists and chemists using some of the most advanced strain-engineering techniques to develop and optimize a novel product in a relatively short time.”