The filamentous fungal genus Aspergillus represents an industrially significant group of eukaryotic microorganisms. For nearly a century, it has been widely utilized in the production of diverse high-value products, including organic acids, industrial enzymes, recombinant proteins, and various bioactive natural compounds. With the rapid advancement of synthetic biology, Aspergillus has been extensively exploited as a heterologous chassis for the production of heterologous proteins (e.g., sweet proteins and antibodies) and the synthesis of natural products (e.g., terpenoids and polyketides) due to its distinct advantages, such as superior protein secretion capacity, robust precursor supply, and efficient eukaryotic post-translational modifications. In this review, we provide a comprehensive summary of the advancements in the successful expression of heterologous proteins and the biosynthesis of natural products using Aspergillus platforms (including Aspergillus niger, Aspergillus nidulans, and Aspergillus oryzae) in recent years. Emphasis is placed on the applications of A. oryzae in the heterologous biosynthesis of terpenoids. More importantly, we thoroughly examine the current state of the art in utilizing CRISPR-Cas9 for genetic modifications in A. oryzae and A. niger. In addition, future perspectives on developing Aspergillus expression systems are discussed in this article, along with an exploration of their potential applications in natural product biosynthesis.

Background: Skin whitening agents often face challenges such as poor stability and low permeability. To overcome these issues, a novel 4-butylresorcinol (4-BR)/D-a- Tocopherol Polyethylene Glycol Succinate (TPGS) deep eutectic solvent (DES) system was developed, which can self-assemble into carrier-free nanoparticles (NPs). Methods: The 4-BR/TPGS DES was synthesized and characterized by theoretical calculations, DSC, FTIR, 1H-NMR, and 2D NMR to confirm its successful formation. Results: The self-assembled 4-BR/TPGS DES NPs showed a 3.46-fold increase in skin permeability, a 1.53-fold improvement in 4-BR stability, a 1.55-fold increase in melanin inhibition in B16 cells, and a 2.16-fold higher melanin suppression in zebrafish compared with traditional 4-BR oil-based formulations. These results indicated the excellent whitening efficacy and transdermal delivery potential of this formulation. Conclusions: The combination of TPGS-based DES and self-assembly technology represents a revolutionary approach for advanced transdermal delivery and the development of skin care products.

Plant-derived bioactive compounds, such as polyphenols and saponins, possess significant pharmacological value. However, conventional extraction methods often suffer from low efficiency, poor bioavailability, and environmental burdens. Aspergillus-based biotransformation has emerged as a superior platform for overcoming these limitations due to their robust secretomes, versatile metabolic networks, and the GRAS (Generally Recognized as Safe) status of specific industrially relevant species (e.g., A. oryzae and A. niger). Existing literature frequently focuses on isolated compounds or general fungal processes. To fill this gap, this review systematically links specific Aspergillus enzymatic systems to an “enzymatic hydrolysis–transformation–synthesis” closed-loop framework, which is essential for industrial-scale valorization. In this review, we summarize recent advances in the biotransformation of phytochemicals by A. niger, A. oryzae, and A. nidulans. These fungi utilize specialized enzymes—including β-glucosidases, cellulases, and glycosidases—to enable precise hydrolysis, deglycosylation, and detoxification under mild conditions. We highlight representative transformations that demonstrate markedly enhanced bioactivity and solubility. Key examples include the conversion of polydatin to resveratrol (>90% yield) and ginsenoside Rb1 to ginsenoside compound K (94.4% conversion rate). Although industrial applications span the food, pharmaceutical, and cosmetic sectors, significant challenges persist in solid-state fermentation (SSF) scale-up, strain stability, target compound over-degradation, and downstream purification. Genetic engineering, process optimization and hybrid bioprocessing are highlighted as promising strategies to overcome these limitations and realize sustainable, high-value production of natural bioactive metabolites.