Enzyme discovery opens a new route to natural UV-absorbing saclipins

Natural UV-absorbing saclipins from the edible cyanobacterium Aphanothece sacrum have promising potential for cosmetic and functional materials, but their low abundance limits their use. Researchers have now identified AsLOX2 as a key gateway enzyme that oxygenates α-linolenic acid to form a saclipin-related intermediate. By combining this enzymatic step with chemical conversion, they produced saclipins A and B, providing a foundation for alternative production methods and a deeper understanding of this unusual natural product pathway.

Ultraviolet (UV)-absorbing compounds from natural sources are attracting interest as potential ingredients for cosmetics and other protective materials. Saclipins A and B are unusual UV-absorbing oxylipins produced by the edible freshwater cyanobacterium Aphanothece sacrum, known in Japan as Suizenji-nori. Although these compounds show promising UV-absorbing and other functional properties, their low natural abundance and poorly understood biosynthesis have limited efforts to use them more broadly. Saclipin accumulation is strongly stimulated by desiccation stress, and the compounds have also been reported to show antioxidative and antiglycative activities as well as photo- and thermochemical stability. Understanding how saclipins are made could therefore help researchers develop production approaches that do not depend entirely on extracting them from the cyanobacterium.

Addressing this challenge, a research team was led by Professor Hakuto Kageyama along with graduate student Yoshie Uchida from the Graduate School of Environmental and Human Sciences, Meijo University, Japan. The researchers searched the A. sacrum genome and identified two candidate lipoxygenase enzymes, AsLOX1 and AsLOX2. They produced recombinant versions of both enzymes and tested their ability to act on α-linolenic acid (ALA), linoleic acid, and arachidonic acid. AsLOX2 showed clear activity toward all three substrates, with the highest activity toward ALA, whereas AsLOX1 showed no detectable activity under the tested conditions. Their findings were published online in the Journal of Natural Products on September 29, 2026.

Further experiments revealed that AsLOX2 acts on ALA in a distinctive way, introducing oxygen at two positions to produce 9,16-diHPOTE, a key intermediate linked to saclipin formation. The researchers confirmed the identity of this intermediate using chromatographic and mass spectrometric analyses. Under optimized conditions, AsLOX2 converted more than 80% of the starting fatty acid into 9,16-diHPOTE within a few minutes, highlighting the enzyme’s strong activity.

“Identifying AsLOX2 as the gateway enzyme gives us an important biochemical entry point for understanding how this unusual UV-absorbing compound is produced,” says Prof. Kageyama.

The team then tested whether 9,16-diHPOTE could be converted into saclipins through a series of chemical reactions. First, the intermediate was reduced to form 9,16-diHOTE. The researchers then used a chemical oxidation step to generate compounds corresponding to saclipins A and B, confirming their identities through comparison with authentic compounds. Saclipin A was produced in greater amounts than saclipin B, with the two occurring at approximately 9:1 ratio. Although the overall yield was modest, the results demonstrated that the enzymatic and chemical steps could be combined to produce these UV-absorbing compounds.

“The combination of an enzymatic gateway step and chemical conversion demonstrates a practical route toward saclipin production, while also highlighting the downstream reactions that remain to be discovered in the natural pathway,” says Prof. Kageyama.

Overall, the study establishes that AsLOX2 performs a key dual oxygenation step that links ALA to the saclipin biosynthetic pathway and demonstrates that saclipins A and B can be produced from the enzyme-derived intermediate through subsequent chemical reactions. The findings provide a foundation for investigating enzymatic, microbial, or other alternative production systems that could reduce reliance on extraction from A. sacrum. However, the authors note that further work is needed to identify the natural downstream enzymes and assess productivity, safety, stability, and other properties before practical cosmetic or functional material applications can be considered. These studies may also clarify how lipid metabolism contributes to stress adaptation.

About Meijo University

Meijo University traces its origin back to the establishment of the Nagoya Science and Technology Course in 1926, giving it a proud history of more than 90 years. As one of the largest universities in the Chubu region, Meijo University is a comprehensive learning institution that supports a wide range of academic fields from the humanities to physical sciences. With a network of more than 200,000 graduates and alumni, it strives to contribute not only to local industries but also to international communities in various fields. Meijo University is also known as the birthplace of the carbon nanotube. To foster the human resources of the next generation, the university continues to tackle ongoing challenges by further enhancing its campus and creating new faculties.

Website: https://www.meijo-u.ac.jp/english/

About Professor Hakuto Kageyama from Meijo University, Japan

Dr. Hakuto Kageyama is a Professor in the Department of Chemistry, Faculty of Science and Technology, Meijo University, Japan. He is also Dean of the Graduate School of Environmental and Human Sciences at Meijo University. He earned his PhD from Nagoya University and received the KOSÉ Cosmetology Award from the KOSÉ Cosmetology Research Foundation in 2021. His research focuses on how cyanobacteria and microalgae adapt to environmental stressors, including desiccation and other environmental challenges. His work explores stress responses, specialized metabolites, and their potential applications, contributing to a better understanding of microbial adaptation and naturally derived functional compounds.

Funding information

This work was supported by Japan Society for the Promotion of Science KAKENHI Grant 24K08623 and a Hibi Science Foundation Grant (to Hakuto Kageyama).