Sinomenine is the main component of the vine Sinomenium acutum. It was first isolated in the early 1920s and has since attracted special interest as a potential anti-rheumatoid arthritis (RA) agent, owing to its successful application in traditional Chinese medicine for the treatment of neuralgia and rheumatoid diseases. In the past few decades, significant advances have broadened our understanding of the molecular mechanisms through which sinomenine treats RA, as well as the structural modifications necessary for improved pharmacological activity. In this review, we summarize up-to-date reports on the pharmacological properties of sinomenine in RA treatment, document their underlying mechanisms, and provide an overview of promising sinomenine derivatives as potential RA drug therapies.

Mogrosides are a group of health-promoting natural products that extracted from Siraitia grosvenorii fruit (Luo-han-guo or monk fruit), which exhibited a promising practical application in natural sweeteners and pharmaceutical development. However, the production of mogrosides is inadequate to meet the need worldwide, and uneconomical synthetic chemistry methods are not generally recommended for structural complexity. To address this issue, an in-fusion based gene stacking strategy (IGS) for multigene stacking has been developed to assemble 6 mogrosides synthase genes in pCAMBIA1300. Metabolic engineering of Nicotiana benthamiana and Arabidopsis thaliana to produce mogrosides from 2,3-oxidosqualene was carried out. Moreover, a validated HPLC-MS/MS method was used for the quantitative analysis of mogrosides in transgenic plants. Herein, engineered Arabidopsis thaliana produced siamenoside I ranging from 29.65 to 1036.96 ng/g FW, and the content of mogroside III at 202.75 ng/g FW, respectively. The production of mogroside III was from 148.30 to 252.73 ng/g FW, and mogroside II-E with concentration between 339.27 and 5663.55 ng/g FW in the engineered tobacco, respectively. This study provides information potentially applicable to develop a powerful and green toolkit for the production of mogrosides.

Crocins are a group of highly valuable water-soluble carotenoids that are reported to have many pharmacological activities, such as anticancer properties, and the potential for treating neurodegenerative diseases including Alzheimer’s disease. Crocins are mainly biosynthesized in the stigmas of food–medicine herbs Crocus sativus L. and Gardenia jasminoides fruits. The distribution is narrow in nature and deficient in resources, which are scarce and expensive. Recently, the synthesis of metabolites in the heterologous host has opened up the potential for large-scale and sustainable production of crocins, especially for the main active compounds crocin I and crocin II. In this study, GjCCD4a, GjALDH2C3, GjUGT74F8, and GjUGT94E13 from G. jasminoides fruits were expressed in Nicotiana benthamiana. The highest total content of crocins in T1 generation tobacco can reach 78,362 ng/g FW (fresh weight) and the dry weight is expected to reach 1,058,945 ng/g DW (dry weight). Surprisingly, the primary effective constituents crocin I and crocin II can account for 99% of the total crocins in transgenic plants. The strategy mentioned here provides an alternative platform for the scale-up production of crocin I and crocin II in tobacco.

Stress on the Endoplasmic reticulum (ER) can severely disrupt cellular function by impairing protein folding and post-translational modifications, thereby leading to the accumulation of poor-quality proteins. However, research on its impact on photosynthesis remains limited. In this study, we investigated the impact of ER stress on the photosynthetic efficiency of Chlamydomonas reinhardtii using pharmacological inducers, tunicamycin (TM) and brefeldin A (BFA), which specifically target the ER. Our measurements of photosynthetic parameters showed that these ER stress-inducing compounds caused a significant decline in photosynthetic efficiency. A proteomic analysis confirmed that TM and BFA effectively induce ER stress, as evidenced by the upregulation of ER stress-related proteins. Furthermore, we observed a widespread downregulation of photosynthesis-related proteins, which is consistent with the results obtained from our measurements of photosynthetic parameters. These findings suggest that the stress on ER has a profound impact on chloroplast function, disrupting photosynthetic processes. This study highlights the critical interdependence between the ER and chloroplasts, and it underscores the broader implications of ER stress on the cellular metabolism and energy efficiency of photosynthetic organisms.

Polyphyllins are the active ingredients of the medicinal plant Paris polyphylla. The biosynthesis of different types of polyphyllins all requires the catalysis of glycosyltransferases. Even though significant efforts have been made to identify PpUGTs capable of catalyzing the initial glycosylation reaction, the specific glycosyltransferases responsible for the synthesis of trillin have not been reported in P. polyphylla. Here, we identified a new trillin synthase, named PpUGT91BP1, which was highly expressed in the rhizome. Importantly, PpUGT91BP1 could specifically glycosylate diosgenin but not pennogenin. To improve its catalytic efficiency, we introduced random mutations through error-prone PCR and conducted an activity-based screening. Three mutants with significantly enhanced trillin synthase activity were identified. Finally, we successfully reconstituted trillin biosynthesis in Nicotiana benthamiana, achieving a yield of 3.69 mg/g of plant dry weight using the mutant PpUGT91BP1. Taken together, our results deepen the understanding of the PpUGT91 family’s role in polyphyllin biosynthesis in P. polyphylla, facilitating rational selection of better P. polyphylla cultivars and guiding future studies in the metabolic engineering of polyphllins.

Natural products from medicinal plants serve as an invaluable resource for drug discovery and development. However, low-abundance natural products are often understudied due to the challenges of obtaining sufficient quantities for pharmacological testing in cells or animals. Additionally, their complex stereochemistry and functional groups make chemical synthesis and purification difficult. In this study, we showcased the power of biosynthetic approaches to explore these underexplored compounds, using the low-abundance polyphyllin trillin 6′-O-glucoside from Paris polyphylla as an example. We identified two trillin 6′-O-glucosyltransferases required for its biosynthesis and successfully reconstructed the entire pathway in Nicotiana benthamiana. We demonstrated that trillin 6′-O-glucoside exhibits anti-bacterial activity comparable to major polyphyllins like polyphyllins I, II, and VII. Notably, it also showed much lower hemolytic activity, a common side effect of those major polyphyllins. Together, our study underscores the advantages of employing biosynthetic approaches to explore natural products that exist in low or trace abundances yet possess equally important pharmacological activities.