An Introduction to Mycosporine-Like Amino Acids

Mycosporine-like amino acids (MAAs) are natural ultraviolet (UV)- absorbing compounds that are attracting attention in the industrial field including cosmetics and pharmaceuticals. This book provides a wide range of descriptions of MAAs, from fundamentals to applications. In order to discuss the properties of MAAs, an understanding of their chemical structures would be required. The purpose of this chapter is to understand the basic molecular structure of MAAs. In general, MAAs have structures in which amino acids are bound to the core structures of cyclohexenone or cyclohexenimine. In addition to the basic structure, the resonance hybrid structures of MAAs are also described here. Delocalization of electrons is considered to affect the stability and the absorption maximum wavelength of MAA molecules. We will also discuss the environmental factors that can affect the structure of MAAs. Finally, databases of molecular structure information of MAAs will be described. 

Accumulation of mycosporine-like amino acids (MAAs) has been reported in a wide range of species in nature, including microalgae, macroalgae, cyanobacteria, phytoplankton, fungi, and some animals. This chapter describes the distribution of MAAs with a focus on macroalgae and cyanobacteria. MAAs biosynthesized by macroalgae have already been applied in cosmetic products, such as Helioguard 365 and Helinori. Macroalgae tend to accumulate multiple types of MAAs, and the types and accumulation levels are affected by changes in environmental factors. Regarding cyanobacteria, we focus on UV, salt, and osmotic stresses, temperature changes, and drought stress as environmental factors, and describe the species in which the accumulations of MAAs are induced by these stresses. UV-B irradiation is a common environmental factor that can induce the accumulation of MAAs in cyanobacteria, but induction by other abiotic stresses has been reported. These findings suggest that MAAs act as a multifunctional molecule that responds to a variety of environmental factors, not just as a UV absorber.

The biosynthetic mechanism of mycosporine-like amino acids (MAAs) has been roughly elucidated. In 2010, the genes responsible for MAA biosynthesis were identified in cyanobacteria. In this chapter, first, we will describe the reaction mechanisms responsible for the biosynthetic pathways of MAAs, mainly based on results from cyanobacteria. Next, as a regulatory mechanism for MAA biosynthesis, the response patterns of MAA accumulation in response to abiotic stresses, such as UV irradiation, salt, and osmotic pressure, will be explained. There are many points to be clarified regarding the detailed regulatory mechanisms, and further analyses are awaited in the future. Because MAAs have useful activities in addition to UV absorption, they are substances that are expected to be used in cosmetics and pharmaceuticals. This chapter also includes discussions from the perspective of future industrial production.

This chapter describes the basics of analytical and preparative methods for mycosporine-like amino acids (MAAs). For samples whose molecular structures are known, high-performance liquid chromatography is widely used as a simple quantitative or qualitative analytical method for MAAs. However, if the molecular structures are unknown, they are often identified by combining several analytical methods, such as liquid chromatography-mass spectrometry and nuclear magnetic resonance analysis. In MAA preparation, the first key factor is how efficiently MAAs can be obtained in the extraction process from biological samples. The second key factor is how efficiently high-purity MAAs can be obtained from the separation process. This chapter also discusses the production of MAAs from an industrial perspective.

In this chapter, we focus on the UV absorption characteristics of MAAs and describe the application examples. UV rays that pass through the ozone layer and the atmosphere and reach the surface of the Earth consist of UV-A and UV-B. Because these rays are harmful to biomolecules, MAAs, which can efficiently absorb these wavelength regions and detoxify their by-products, are promising natural organic compounds such as sunscreens. Products containing MAAs extracted from red algae are already on the market. With a focus on Helioguard 365 and HELINORI, the biological effects of MAAs against UV irradiation will be described.

 It is known that the generation of reactive oxygen species (ROS) caused by UV irradiation and oxidative reactions accelerate skin aging. Substances that suppress or eliminate the generation of ROS are called antioxidants. So far, various mycosporine-like amino acids (MAAs) have been reported to have antioxidative activities. To prevent damage to the skin caused by ROS and maintain the homeostasis of the epidermis, skin cells have an endogenous antioxidant system consisting of enzymatic reactions. Although many points are unclear about the regulatory mechanisms, it has been suggested that MAAs are involved in the regulation of genes encoding enzymes that are involved in this system. This chapter provides a comprehensive overview of the antioxidant activities of MAAs. 

Inflammation is the defensive reaction system that occurs when the body receives a harmful stimulus and tries to remove it. In general, the area where the reaction occurs has a fever, swelling, redness, and pain. The stimuli that cause inflammation are diverse but include UV irradiation and reactive oxygen species. This chapter briefly describes the inflammatory response pathways caused by these stimuli. After that, it outlines the effects of mycosporine-like amino acids (MAAs) on the accumulation, activity, and regulation of factors contained in the inflammatory pathway. Although research findings are accumulating, the molecular mechanisms are still unknown. Details of the relationship between the molecular structures of MAAs and their functions in the inflammatory pathway await further study.

Advanced glycation end products (AGEs) are formed by a series of chemical reactions initiated by non-enzymatic glycation reactions. In this process, the reducing sugar binds to the free amino group of the protein. The formation of AGEs that accompany the aging process is thought to be associated with various diseases such as diabetes and Alzheimer's disease. A number of inhibitors derived from synthetic compounds and natural products have been developed and evaluated to prevent the formation of AGEs. Compared to synthetic compounds, natural products are considered to be relatively safe for human consumption, so there is an increasing demand for compounds derived from natural products. From this perspective, this chapter focuses on mycosporine-like amino acids as naturally occurring inhibitors against AGEs formation. 

Enzymes involved in the degradation of the extracellular matrix (ECM) are deeply involved in skin aging. Compounds that suppress the degradation of collagen and elastin, constituents of the ECM, are of significant value to the cosmetics field. So far, more than 10 types of MAAs have been reported to inhibit the activity of collagenase, which belong to the family of matrix metalloproteinases. It has been suggested that the metal-chelating activity of MAAs is involved in these mechanisms of action. However, MAAs have not been reported to have an inhibitory activity on elastase. This chapter briefly summarizes these observations.

As mentioned in Chapters 8 and 9, the useful functions of MAAs, such as the anti-glycative property and collagenase inhibitory activity, might be associated with their metal chelating activity. Although there are few reports on the metal-chelating activity of MAAs, a chelating model of MAAs and metal ions has recently been proposed. This chapter briefly summarizes these observations.

This chapter describes the research findings on the DNA protection, wound healing, and anti-cancer effects of MAAs and their use in horticulture and as a raw material for film-type UV-blocking materials. These applications are additional to the use of MAAs as sunscreen agents and pharmaceuticals applied to humans.