Using robotic evolution, UC San Diego scientists have trained bacteria to produce more pigment that powers the octopus' camouflage.
Genetic analysis revealed key mutations that turned the microbes into highly efficient pigment factories.
Cracking nature's camouflage secret
Researchers at the University of California, San Diego have taken a major step toward understanding one of nature's most remarkable gifts: the ability to disappear in plain sight.
Octopuses, squid, cuttlefish, and their cephalopod relatives are famous for their incredible camouflage abilities, rapidly changing the color and texture of their skin to adapt to their surroundings. This natural trick relies on a complex pigment called xanthommatin, which controls many of the animals' color changes.
For decades, scientists and even defense researchers have been fascinated by xanthommatin's color-changing potential. However, reproducing the pigment in the laboratory has so far proven to be extremely difficult.
Produce nature's camouflage pigment at scale
In a new study, a team from UC San Diego's Scripps Institution of Oceanography reports a major advance in understanding how nature creates camouflage. Researchers developed a new method for producing xanthommatin in large quantities, making it possible to study and use this elusive pigment more easily than ever before.
Their bio-inspired method created the pigment inside bacteria, achieving yields up to 1,000 times higher than previous approaches. This breakthrough could enable a range of applications, from sustainable dyes and UV-blocking materials to advanced coatings and photoelectronic devices.
Technical bacteria for the production of cephalopod pigments
“We have developed a new technique that has accelerated our ability to produce a material, in this case xanthommatin, in a bacterium for the first time,” said Bradley Moore, the study's senior author and a marine chemist with joint appointments at Scripps Oceanography and the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. “This natural pigment gives an octopus or squid the ability to camouflage itself – a fantastic superpower – and our success in advancing the production of this material is just the tip of the iceberg.”
Published on November 3rd in Natural biotechnologythe research was supported by the National Institutes of Healththe Office of Marine Research, the Swiss National Science Foundation and the Novo Nordisk Foundation.
According to the authors, this discovery doesn't just explain the chemistry behind nature's color-changing wonders. The same biotechnology could be applied to other useful compounds, helping industries shift from petroleum-based production to sustainable, nature-derived materials.
From the squid ink to the butterfly wings
Over and beyond CephalopodsXanthommatin is also found in insects in the arthropod group and contributes to the bright orange and yellow tones of the wings of monarch butterflies and the bright reds seen in dragonfly bodies and fly eyes.
Despite xanthommatine's fantastic color properties, it remains poorly researched due to ongoing supply difficulties. Obtaining the pigment from animals is neither scalable nor efficient, and traditional laboratory methods are labor-intensive and rely on low-yield chemical synthesis.
Researchers in Scripps Oceanography's Moore Lab wanted to change that and collaborated with colleagues at UC San Diego and the Novo Nordisk Foundation Center for Biosustainability in Denmark to develop a solution, a type of growth feedback loop, that they call “growth-coupled biosynthesis.”
Causing bacteria to produce camouflage chemistry
The way they bioengineered the octopus pigment, a chemical, in a bacterium represents a novel departure from typical bioengineering approaches. Their approach closely linked the production of the pigment to the survival of the bacterium that produced it.
“We needed a completely new approach to address this problem,” said Leah Bushin, lead author of the study, now a faculty member at Stanford University and formerly a postdoctoral fellow in the Moore Lab at Scripps Oceanography, where her work was conducted. “Essentially, we found a way to get the bacteria to make more of the material we needed.”
When researchers try to get a microbe to produce a foreign compound, it usually results in significant metabolic stress. Without significant genetic manipulation, the microbe is reluctant to divert its vital resources to produce something unknown.
Linking life with pigment production
By linking the cell's survival to the production of its target compound, the team was able to trick the microbe into producing xanthommatin. To do this, they started with a genetically engineered “sick” cell that could only survive if it produced both the desired pigment and a second chemical called formic acid acid. For every pigment molecule produced, the cell also produced a molecule of formic acid. The formic acid, in turn, provides fuel for cell growth and creates a self-sustaining cycle that drives pigment production.
“We made sure that the activity through this pathway, the production of the compound of interest, is absolutely vital. If the organism doesn't produce xanthommatin, it doesn't grow,” Bushin said.
Bioengineering meets evolution
To further improve the cells' ability to produce the pigment, the team used robots to develop and optimize the engineered microbes through two high-throughput adaptive laboratory evolution campaigns developed by study co-author Adam Feist, a professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering and a senior scientist at the Novo Nordisk Foundation Center for Biosustainability. The team also used custom bioinformatics tools from the Feist lab to identify key genetic mutations that increased efficiency and allowed the bacteria to produce the pigment directly from a single nutrient source.
“This project provides a glimpse into a future in which biology enables the sustainable production of valuable compounds and materials through advanced automation, data integration and computational design,” said Feist. “Here we show how we can accelerate innovation in bioproduction by bringing together engineers, biologists and chemists and leveraging some of the most advanced stem engineering techniques to develop and optimize a novel product in a relatively short period of time.”
Record-breaking pigment production
Previous attempts to produce the pigment were notoriously inefficient, typically producing only about five milligrams per liter, “if you're lucky,” Bushin said. The new technology changed this dramatically, increasing output to one to three grams per liter – an improvement of about a thousandfold.
Although the project required several years of careful planning and experimental design, success came surprisingly quickly once the experiments began.
“It was one of my best days in the lab,” Bushin recalled of the breakthrough. “I set up the experiment and left it overnight. When I came in the next morning and found that it worked and produced a lot of pigment, I was thrilled. Moments like these are why I get into science.”
Nature-inspired manufacturing for the future
Moore believes this nature-inspired, non-invasive approach could revolutionize the production of biochemicals.
“We have really changed the way people think about how to engineer a cell,” he said. “Our innovative technological approach has triggered a huge leap in production capacity. This new method solves a supply problem and could now make this biomaterial much more widely available.”
From camouflage to cosmetics
While some of the potential uses may seem futuristic, interest is already growing in several industries. Both the U.S. Department of Defense and cosmetics companies are studying the material's potential. Defense researchers are drawn to its natural camouflage ability, while skin care developers explore its promise for eco-friendly sunscreen. Other possible applications include color-changing paints, smart coatings and environmental sensors.
“As we look to the future, people will want to rethink how we make materials to support our synthetic lifestyles of 8 billion people on Earth,” Moore said. “Thanks to federal funding, we have opened up a promising new avenue for developing nature-inspired materials that are better for people and planet.”
Source: “Growth-coupled microbial biosynthesis of animal pigment November 3, 2025, Natural biotechnology.
DOI: 10.1038/s41587-025-02867-7
Other study authors include Tobias Alter, María Alván-Vargas, Daniel Volke, Òscar Puiggené and Pablo Nikel from the Novo Nordisk Foundation Center for Biosustainability; Elina Olson of the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego; Lara Dürr and Mariah Avila from Scripps Institution of Oceanography at UC San Diego; and Taehwan Kim and Leila Deravi of Northeastern University.
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