Recent progress in unraveling the biosynthesis of natural sunscreens mycosporine-like amino acids

Abstract

Exposure to ultraviolet (UV) rays is a known risk factor for skin cancer, which can be notably mitigated through the application of sun care products. However, escalating concerns regarding the adverse health and environmental impacts of synthetic anti-UV chemicals underscore a pressing need for the development of biodegradable and eco-friendly sunscreen ingredients. Mycosporine-like amino acids (MAAs) represent a family of water-soluble anti-UV natural products synthesized by various organisms. These compounds can provide a two-pronged strategy for sun protection as they not only exhibit a superior UV absorption profile but also possess the potential to alleviate UV-induced oxidative stresses. Nevertheless, the widespread incorporation of MAAs in sun protection products is hindered by supply constraints. Delving into the biosynthetic pathways of MAAs can offer innovative strategies to overcome this limitation. Here, we review recent progress in MAA biosynthesis, with an emphasis on key biosynthetic enzymes, including the dehydroquinate synthase homolog MysA, the adenosine triphosphate (ATP)-grasp ligases MysC and MysD, and the nonribosomal peptide synthetase (NRPS)-like enzyme MysE. Additionally, we discuss recently discovered MAA tailoring enzymes. The enhanced understanding of the MAA biosynthesis paves the way for not only facilitating the supply of MAA analogs but also for exploring the evolution of this unique family of natural sunscreens.

One-sentence summary: This review discusses the role of mycosporine-like amino acids (MAAs) as potent natural sunscreens and delves into recent progress in their biosynthesis.

Keywords: Biosynthesis; Mycosporine-like amino acids; Sunscreen.

Graphical Abstract

Fig. 1.

MAAs as natural sunscreens. (A) Chemical structures of selected MAAs with corresponding maximal absorbance wavelengths and extinction coefficients. (B) Representative steps of the ultrafast deexcitation pathway of MAAs involving significant structural changes.

Fig. 2.

Synthetic routes of MG starting from d-(-)-quinic acid in 13 steps (A) and MAA derivatives lacking a stereocenter at C5 within five steps (B).

Fig. 3.

A general MAA biosynthetic pathway catalyzed by MysA-E and MysH (A) and the diversity of MAA BGCs in different organisms (B).

Fig. 4.

MysA initiates the MAA biosynthesis. (A) Superimposing the active sites of MysA (PDB ID 5TPR, cyan) and EEVS (PDB ID 4P53, grey) revealed the difference of three residues. Zinc ion (Zn²⁺) was shown as a dark grey sphere. The cofactor NAD⁺ was shown as sticks with backbone carbons colored according to corresponding structures. (B) Proposed MysA reaction pathway starting from SH-7-P. The figure is modified from the previous work (Osborn et al., 2017).

Fig. 5.

ATP-grasp enzymes MysC and MysD respectively decorate C3 and C1 of the MAA scaffold. (A) MysC reaction pathway involving C3-phosphorylation. (B) MysC and MysD homologs synthesize multicore MAAs. (C) Proposed MysD reaction pathway.

Fig. 6.

MysE modifies the C1 of MG, producing disubstituted MAA analogs. (A) Proposed reaction mechanism of MysE involving ATP-dependent amino acid loading. (B) Domain organization of representative MysE homologs identified from cyanobacterial genomes.