The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots

Lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human health. Elucidating the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant improvement. Here, we identified the complete pathway to stereoselectively synthesize antiviral (-)-lariciresinol glucosides in Isatis indigotica roots, which consists of three-step sequential stereoselective enzymes DIR1/2, PLR, and UGT71B2. DIR1 was further identified as the key gene in respoJanuary 2024nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan content. Mechanistically, the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of DIR1. These systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2 to stereoselectively synthesize (-)-lariciresinol derived antiviral lignans in I. indigotica roots and is also a part of the LTF1-mediated regulatory network to resist stresses. In conclusion, the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

The stereoselective synthesis of privileged epimer of C-10 carba artemisinins and the effect of substituted groups with different acid-base properties on the antimalarial activity / 药学学报

Artemisinin is a sesquiterpene lactone natural product that contains an endoperoxide bond. Artemisinin has various biological activities including antimalarial, anti-tumor, antiviral and anti-fibrotic activity. Owing to the poor pharmacokinetic properties of artemisinin, its derivatives are currently used in clinic and frequently reported in literature. Although numerous derivatives of artemisinin have been reported, no study has been carried out yet to study the effect of substituted groups with different acid-base property on the antimalarial activity. Among these derivatives, the C-10 carbon artemisinin derivatives are often reported, and their corresponding 10β epimer show much better antimalarial activity than 10α epimer with large-sized substitute. However, there is currently no stereoselective synthesis to efficiently prepare the privileged 10β epimer of C-10 carba artemisinin. To address these two scientific questions, we herein first report an optimized method to stereoselectively synthesize the 10β epimer of C-10 carba artemisinin (98∶2 d.r.). Second, we employed the optimized method to synthesize a series of C-10 carba artemisinin derivatives with different acid-base properties. The antimalarial examination indicated that those derivatives with neutral groups or basic group of short chain showed similar antimalarial activity as dihydroartemisinin (DHA). The acidic group could dramatically decrease the antimalarial effect and was more than 22-fold less effective than DHA or the neutral ones. This study will shed light on the development of new generation of artemisinin derivatives with potent activity.