Selenium (Se) is an essential trace element required by plants and animals. Se exists as the active center of numerous antioxidant enzymes in the form of selenocysteine [1]. It plays a vital role in anti-oxidation and energy metabolism, as well as various functions such as immune regulation, virus mutation suppression, and reduction of viral pathogenicity [2]. However, Se has a narrow range between its toxic dose (> 400 μg per day) and the deficiency level of dietary intake (< 40 μg per day) compared to other micronutrients [3]. Se naturally occurs in different forms, including selenide [Se (-II)], elemental Se [Se (0)], selenite [Se (IV)], and selenate [Se (VI)]. Studies have shown that in mice, SeNPs (selenium nanoparticles) exhibit significantly lower acute toxicity compared to other forms of Se [4], [5], [6]. Furthermore, SeNPs have demonstrated remarkable anticancer, antioxidant, antibacterial, and anti-biofilm properties [7], [8], [9]. They have also exhibited potent antimicrobial activity against pathogenic bacteria and fungi [10], [11].

The microbial synthesis of SeNPs offers several advantages over physical and chemical methods, including higher absorption rates, lower toxicity, and greater stability [12]. Fungi and yeast have the ability to produce metal nanoparticles and nanostructures by utilizing reducing enzymes, both intracellularly and extracellularly [13]. Yeast, in particular, holds an advantage over bacteria in the biological production of nanoparticles due to its high tolerance and bioaccumulation capabilities [14]. Within yeast cells, tetravalent selenium undergoes a spontaneous reaction with reduced glutathione (GSH), leading to the formation of glutathionylselenol (GS-Se-H) and oxidized glutathione (GSSG). Subsequently, GS-Se-H undergoes further transformations, resulting in the formation of elemental selenium and GSH (Fig. 1) [15], [16]. Additionally, Zhang et al. [17] discovered that S. cerevisiae cells excrete SeNPs through vesicle-like structures in a microaerophilic environment.

In previous studies, various microbial strains have been found to synthesize SeNPs. However, there is limited research on the regulation of SeNP production and stability in yeast. To address this gap, our study focuses on a genetically modified strain of S. cerevisiae, aiming to enhance SeNP production and investigate the identification, analysis, and overexpression of surface proteins associated with SeNPs. Additionally, we explore the impact of overexpressed SeNPs surface proteins on the stability of SeNPs. This research aims to establish an efficient method for yeast to synthesize SeNPs with high stability across different pH and temperature conditions. The findings of this study hold significant potential for applications in nanomedicine and nutritional supplements to address selenium deficiency.