We have nearly figured out the secrets of one of nature's true "superpowers"

UC San Diego engineers bacteria to mass-produce camouflage pigment, enabling sustainable biomaterials and advancing bio-inspired technologies.

Scientists at the University of California San Diego have developed a new way to produce large amounts of xanthommatin, a natural pigment that helps octopuses, squids and other cephalopods rapidly change the color of their skin for camouflage. The advance could help researchers better understand how these animals change color while making the pigment easier to produce for research and future applications.

The findings, published on Nov. 3 in Nature Biotechnology, were led by researchers at the UC San Diego Scripps Institution of Oceanography. The work was supported by the National Institutes of Health, the Office of Naval Research, the Swiss National Science Foundation and the Novo Nordisk Foundation.

Xanthommatin is a naturally occurring pigment found in cephalopods, where it helps them quickly change the color of their skin by altering how light is absorbed and reflected. It is also found in insects, giving monarch butterflies their orange and yellow wing colors and contributing to the red coloration of dragonflies and fly eyes.

Scientists have been interested in xanthommatin for years because of its unique color-changing properties. However, studying it has been difficult because it is hard to produce in large quantities. Collecting the pigment from animals is not practical, while traditional laboratory methods produce only small amounts and require a lot of time and effort. Existing methods for making complex natural compounds in bacteria also usually start with very low production, meaning researchers have to spend years improving the process.

To solve this problem, the research team turned to Pseudomonas putida, a harmless soil bacterium that is commonly used in biotechnology because it can be engineered to make useful chemicals. Instead of simply adding the genes needed to produce xanthommatin, the scientists redesigned the bacteria so they could only grow if they made the pigment.

The method, called "growth-coupled biosynthesis," links the bacteria's survival directly to xanthommatin production. As the bacteria produce the pigment, they also make formic acid, a simple chemical that the engineered cells need to grow. This creates a self-sustaining cycle where the bacteria continue producing the pigment because their survival depends on it.

"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, the study's senior author and a marine chemist with appointments at Scripps Oceanography and the 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."

The researchers said this approach is different from many existing methods of engineering bacteria, which often place too much stress on the cells by making them produce compounds they do not naturally make. Because of that, production is usually very low and researchers have to go through many rounds of testing and genetic changes before the process becomes useful.

"We needed a whole new approach to address this problem," said Leah Bushin, the study's lead author, who conducted the research as a postdoctoral researcher at Scripps Oceanography and is now a faculty member at Stanford University. "Essentially, we came up with a way to trick the bacteria into making more of the material that we needed."

Bushin added, "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."

After building the system, the researchers improved it further using adaptive laboratory evolution, a process where bacteria are grown over many generations so the best-performing cells naturally become more common. They also used automated laboratory systems and computer-based analysis to identify genetic changes that boosted pigment production and allowed the bacteria to make xanthommatin directly from glucose, a common sugar used as a food source for microbes.

The new method increased production from about five milligrams of pigment per liter using traditional techniques to between one and three grams per liter. That is up to 1,000 times more than previous methods.

"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 Adam Feist, a study co-author and professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering. "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."

The researchers believe the same growth-coupled approach could also be used to produce other complex natural compounds that are currently difficult to make in bacteria. If successful, it could provide a simpler and more efficient way to produce naturally occurring materials while reducing reliance on fossil fuel-based manufacturing.

Bushin recalled seeing the results for the first time during the experiments. "It was one of my best days in the lab," she said. "I'd set up the experiment and left it overnight. When I came in the next morning and realized it worked and it was producing a lot of pigment, I was thrilled. Moments like that are why I do science."

According to the researchers, collaborators are already exploring possible uses for xanthommatin in products such as natural sunscreens, thermal coatings, dyes, environmental sensors and materials with color-changing properties. Moore said the production method could also change how scientists engineer bacteria to produce other valuable biological compounds.

"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."

TD;DR

• Scientists at UC San Diego developed a new way to produce xanthommatin, the natural pigment that allows octopuses, squids, and other cephalopods to rapidly change their skin color for camouflage—a remarkable ability often described as a biological "superpower."

• Instead of simply inserting the required genes, the researchers engineered Pseudomonas putida bacteria so that they could only survive if they produced xanthommatin, using a novel growth-coupled biosynthesis approach that links pigment production directly to bacterial growth.

• By further optimizing the bacteria through adaptive laboratory evolution, automation, and computational analysis, the team enabled them to efficiently produce xanthommatin from glucose, a simple sugar.

• The technique boosted pigment production from about 5 mg/L to 1–3 g/L—an improvement of up to 1,000 times over previous methods.

• The breakthrough removes a major supply bottleneck for studying xanthommatin and could make it much easier to manufacture other complex natural compounds using engineered microbes.

• Beyond research, the pigment is already being explored for applications such as natural sunscreens, smart color-changing materials, thermal coatings, dyes, and environmental sensors, while the production strategy could transform how valuable biomaterials are manufactured sustainably.

   

Source: University of California, Nature

This article was generated with some help from AI and reviewed by an editor. Under Section 107 of the Copyright Act 1976, this material is used for the purpose of news reporting. Fair use is a use permitted by copyright statute that might otherwise be infringing.

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