The functional pool of canonical amino acids (cAAs) has been enriched through the emergence of non-canonical amino acids (ncAAs). NcAAs play a crucial role in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis due to its environmental friendliness and high efficiency. The breakthrough genetic code expansion (GCE) technique developed in recent years has allowed the incorporation of ncAAs into target proteins, giving them special functions and biological activities. The biosynthesis of ncAAs and their incorporation into target proteins within a single microbe has become an enticing application of such molecules. Based on that, in this study, we first review the biosynthesis methods for ncAAs and analyze the difficulties related to biosynthesis. We then summarize the GCE methods and analyze their advantages and disadvantages. Further, we review the application progress of ncAAs and anticipate the challenges and future development directions of ncAAs.

Acanthopanax sessiliflorus (Rupr. & Maxim.) Seem. (Araliaceae) is one of the most abundant species of genus Acanthopanax. The fruits of A. sessiliflorus are used in traditional medical protocols as an analgesic, tonic, antidiabetic, antihypertensive, anti-inflammatory, antitumor, and immune-stimulating agent. In this work, we carried out a comprehensive investigation into the anthocyanin components in the fruits of A. sessiliflorus. The anthocyanin content in the fresh fruits of A. sessiliflorus was determined by high performance liquid chromatography-diode array detection (HPLC/DAD), and the anthocyanin component was isolated from these using high-speed counter-current chromatography (HSCCC) and elucidated by electro-spray ionization-mass spectrometry (ESI/MS), ¹H- and ¹³C-NMR. Its antioxidant activity was evaluated by ferric-reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). We found that A. sessiliflorus contained a gross anthocyanin content of 121.35 mg/100 g. HSCCC was successfully used for separation and purification of the primary anthocyanin component, cyanidin 3-xylosyl-galactoside. The antioxidant and radical scavenging tests indicated that cyanidin 3-xylosyl-galactoside is a potent antioxidant.

Metal organic frameworks (MOFs) are formed by self-assembly of metal ions and organic ligands. A special type of MOF called ZIF-8, which is formed by self-assembly of zinc ions and 2-methylimidazole, shows excellent stability in aqueous solutions and disintegrates under acidic conditions. These properties make ZIF-8 a suitable carrier material for pH-stimulated drug delivery systems. Glabridin is an isoflavane compound that is widely present in the roots of licorice. Because of its outstanding skin whitening properties, glabridin is widely used as a whitener in the cosmetics industry. In this study, ZIF-8 was employed to encapsulate glabridin. Glabridin-loaded ZIF-8 was successfully prepared with a drug encapsulation efficiency of 98.67%. The prepared sample showed a fusiform or cruciate flower-like structure, and its size was about 3 μm. ZIF-8 enabled pH-controlled release of glabridin. Moreover, ZIF-8 encapsulation significantly enhanced the intracellular anti-oxidant activity and melanogenesis inhibitory activity of glabridin. This study provides a new approach that shows great potential to improve the biological application of glabridin.

Natural products possess potent pharmacological activities and health benefits. However, drawbacks such as water insolubility, poor stability, and low bioavailability limit their practical applications. This research is dedicated to the development of suitable natural self-assembled nano-delivery systems to encapsulate natural molecule drugs, improving their dispersion and stability in aqueous solution. As a model drug, curcumin (Cur) was encapsulated in zinc–adenine nanoparticles (Zn–Adenine), based on the self-assembly of a coordination matrix material. Hyaluronic acid (HA) was further functionalized on the surface of Cur@(Zn–Adenine) to realize a tumor-targeted delivery system. The morphology was characterized through TEM and zeta potential analyses, while the encapsulation mechanism of the nanoparticles was researched via XRD and FTIR. The formed Cur@(Zn–Adenine)@HA nanoparticles exhibited good drug loading efficiency and drug loading rate. Moreover, compared to free Cur, Cur-loaded (Zn–Adenine)@HA showed enhanced pH stability and thermal stability. In particular, Cur@(Zn–Adenine)@HA demonstrated excellent biocompatibility and strong specificity for targeting CD44 protein on cancer cells. The above results indicate that (Zn–Adenine)@HA NPs can serve as an effective nano-delivery system for hydrophobic substances.

The emergence of non-canonical amino acids (ncAAs) has enriched the functional pool inherent in canonical amino acids (cAAs). ncAAs are important building blocks in the production of various pharmaceuticals. The biosynthesis of ncAAs has emerged as an alternative to traditional chemical synthesis because of its environmental friendliness and high efficiency. The breakthrough genetic code expansion (GCE) technique developed in recent years has allowed for the incorporation of ncAAs into target proteins, giving them special functions and biological activities. Biosynthesis of ncAAs and their incorporation into target proteins within a single microbe has become an enticing application of such molecules. Based on that, in this study we first review the biosynthesis methods for ncAAs and analyze the difficulties in biosynthesis. We then summarize the GCE methods and analyze their advantages and disadvantages. Further, we review the application progress of ncAAs and anticipate the challenges and future development directions of ncAAs.