Scientists at the University of California San Diego have developed a new method to produce large quantities of xanthommatin, the pigment responsible for the color-changing abilities in octopuses and other cephalopods. This breakthrough could expand the pigment’s use in various industries, including cosmetics, electronics, and materials science.
Xanthommatin enables animals such as octopuses, squids, and cuttlefish to blend into their surroundings by changing their skin color. The pigment has been difficult to study because it is hard to obtain in sufficient amounts using traditional methods.
The research team from UC San Diego’s Scripps Institution of Oceanography reported that they were able to generate up to 1,000 times more xanthommatin than previous approaches by engineering bacteria to produce it. Their work was published on November 3 in Nature Biotechnology and supported by several organizations including the National Institutes of Health and the Office of Naval Research.
“We’ve developed a new technique that has sped up our capabilities to make a material, in this case xanthommatin, in a bacterium for the first time,” said Bradley Moore, senior author of the study and marine chemist with appointments at Scripps Oceanography and UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. “This natural pigment is what gives an octopus or a squid its ability to camouflage — a fantastic superpower — and our achievement to advance production of this material is just the tip of the iceberg.”
Beyond marine animals, xanthommatin also contributes colors found in insects like monarch butterflies and dragonflies. Historically, harvesting xanthommatin from animal sources has not been scalable or efficient. Chemical synthesis methods are also labor-intensive with low yields.
To address these challenges, researchers used an approach called “growth coupled biosynthesis.” They engineered bacteria so that their survival depended on producing both xanthommatin and formic acid. For every molecule of pigment made, one molecule of formic acid was also produced; formic acid fueled cell growth, creating a feedback loop that drove higher pigment production.
“We needed a whole new approach to address this problem,” said Leah Bushin, lead author now at Stanford University who conducted her work as a postdoctoral researcher at Scripps Oceanography. “Essentially, we came up with a way to trick the bacteria into making more of the material that we needed.”
Bushin explained that without significant genetic changes microbes usually resist producing foreign compounds due to metabolic burden. By linking cell survival directly with compound production, researchers overcame this resistance.
The team further optimized bacterial strains using robotics-driven adaptive laboratory evolution campaigns developed by Adam Feist’s lab at UC San Diego Jacobs School of Engineering and Novo Nordisk Foundation Center for Biosustainability. Custom bioinformatics tools helped identify genetic mutations increasing efficiency so bacteria could make pigment 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.”
Traditional methods yield only about five milligrams per liter; according to Bushin, their process produces between one to three grams per liter—a substantial improvement.
Moore noted potential interest from defense agencies exploring camouflage applications as well as skincare companies interested in natural sunscreens made from xanthommatin. Other possible uses include color-changing paints or environmental sensors.
“We’ve really disrupted the way that people think about how you engineer a cell,” Moore said. “Our innovative technological approach sparked a huge leap in production capability. This new method solves a supply challenge and could now make this biomaterial much more broadly available.”
“As we look to the future, humans will want to rethink how we make materials to support our synthetic lifestyle of 8 billion people on Earth,” added Moore. “Thanks to federal funding, we’ve unlocked a promising new pathway for designing nature-inspired materials that are better for people and the planet.”
Other contributors included scientists from UC San Diego departments as well as international partners at Northeastern University and Denmark’s Novo Nordisk Foundation Center for Biosustainability.
