The Melanized Microbes for Multiple Uses in Space Project, known as MELSP, launched to the International Space Station in November 2023 to test how low Earth orbit conditions affect engineered microorganisms that synthesize melanin. Melanin is a multifunctional biopolymer valued for its radiation shielding, antioxidant activity, and thermal stability, and is a candidate product for in situ resource use during deep space exploration.

In the MELSP study, Naval Research Laboratory teams flew engineered strains of Escherichia coli that produce melanin using a tyrosinase enzyme pathway, and matched them with identical ground based controls. The goal was to track how spaceflight conditions influence growth, enzyme activity, and overall melanin yield compared to performance in standard laboratory conditions on Earth.

The researchers found that microbes on the orbital platform still produced melanin, but they did so much less efficiently than the same strains cultured on the ground. Despite active tyrosinase enzymes, the space grown bacteria generated significantly lower levels of pigment, indicating that constraints emerged elsewhere in the production system rather than in the basic biosynthetic machinery itself.

"Our findings show that microgravity doesn't simply slow microbial growth, it rewires how cells move nutrients, manage stress, and allocate metabolic resources," said Zheng Wang, principal investigator of MELSP and a research biologist at the Naval Research Laboratory's Center for Bio/Molecular Science and Engineering. "These constraints must be addressed if microbes are to reliably manufacture materials, medicines, or life-support components during long-duration missions."

Follow on biochemical, proteomic, and metabolomic studies pointed to a bottleneck in the transport and use of tyrosine, the molecular precursor required for melanin synthesis. While the engineered cells still expressed the components needed to make melanin, they struggled to move tyrosine into place and channel it through the pathway under spaceflight conditions.

"Microgravity alters fluid behavior, leading to altered growth rates and phenotypes in the space environments," said Tiffany Hennessa, a research biologist in the Laboratory for Molecular Interfaces and co principal investigator of MELSP. "Our data indicate that under these conditions, cells struggle to efficiently import and process key substrates, even when the biosynthetic machinery itself remains intact. The machinery inside the cell was there, but the inputs weren't getting to where they needed to be, and that directly impacted melanin production."

Proteomic measurements showed that bacteria grown on the orbiting platform increased production of multiple stress response proteins, including systems linked to oxidative stress, respiration, and DNA repair. Metabolomic profiling documented higher levels of stress related molecules such as trehalose, together with depleted glutathione, a central player in maintaining redox balance inside cells.

"We saw increased production of stress-related proteins and chemicals associated with stress responses," Hennessa said. "That tells us the cells were under pressure in the space environment, and when that happens, survival becomes a higher priority than producing extra biomaterials."

To confirm that these effects were driven by microgravity related forces rather than an isolated feature of the space station environment, the Naval Research Laboratory team partnered with researcher Cheryl Nickerson and her group at Arizona State University. Using a Rotating Wall Vessel bioreactor to simulate low shear microgravity conditions on Earth, they reproduced the key findings, including reduced melanin production, altered metabolism, and lower microbial viability.

"This study provides a critical reality check for space biomanufacturing," Wang said. "Engineering microbes for space isn't just about genes and enzymes, it's about designing systems that account for transport, stress, and physical forces unique to the space environment."

According to the investigators, viewing engineered microbes as small cell factories helps clarify the design challenges. When these factories operate in microgravity, they must manage disrupted fluid dynamics, persistent stress, and impaired nutrient movement while still delivering high yields of target products, making system level optimization essential.

"These are essentially little cell factories," Hennessa said. "If we can figure out how to help them manage stress and move nutrients more efficiently, we can make biomanufacturing in space far more reliable."

The MELSP results provide design guidance for future efforts to build resilient, high yield microbial production systems for deep space missions. Strategies under consideration include reengineering transport pathways, reducing metabolic burden from production constructs, and developing bioreactors that offset the loss of gravity driven mixing and mass transport.

By clarifying how microgravity reshapes microbial metabolism and stress responses, the study adds to a growing body of work that will inform NASA's Artemis campaign and broader Department of War initiatives aimed at sustained human operations beyond low Earth orbit. Reliable biological manufacturing platforms are expected to play a central role in producing materials, therapeutics, and consumables far from terrestrial supply chains.

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