Efficient heterologous biosynthesis of verazine,a metabolic precursor of the anti-cancer drug cyclopamine,in Nicotiana benthamiana

Dear Editor,Among the large number of Veratrum steroid alkaloids(Zhang et al.,2020),cyclopamine has been shown to have various inhibitory mechanisms against cancer,including inhibition of the hedgehog signaling pathway,improvement of tumor tissue microenvironment,inhibition of cell respiration,promotion of cell apoptosis,and reversal of tumor drug resistance(Liu et al.,2023).The biosynthetic pathway of verazine,a possible metabolic precursor of cyclopamine,has been discovered in Veratrum californicum(Augustin et al.,2015).However,the content of Veratrum steroid alkaloids in plants is very low(Supplemental Figure 2),so reliance on direct extraction from plants for commercial production is not feasible.A more effective strategy is to synthesize rare plant secondary metabolites using synthetic biology technology(Liu et al.,2022).

Transgenic japonica rice expressing the cry1C gene is resistant to striped stem borers in Northeast China

Rice production and quality are seriously affected by the lepidopteran pest,striped stem borer(SSB),in Northeast China.In this study,a synthetic cry1 C gene encoding Bacillus thuringiensis(Bt)δ-endotoxin,which is toxic to lepidopteran pest,was transformed into a japonica rice variety(Jigeng 88)in Northeast China by Agrobacterium-mediated transformation.Through molecular detection and the Basta resistance germination assay,a total of 16 single-copy homozygous transgenic lines were obtained from 126 independent transformants expressing cry1 C.Finally,four cry1 C-transgenic lines(JL16,JL23,JL41,and JL42)were selected by evaluation of the Cry1 C protein level,insect-resistance and agronomic traits.The cry1 C-transgenic lines had higher resistance to SSB and higher yield compared with non-transgenic(NT)control plants.T-DNA flanking sequence analysis of the transgenic line JL42 showed that the cry1 C gene was inserted into the intergenic region of chromosome 11,indicating that its insertion may not interfere with the genes near insertion site.In summary,this study developed four cry1 C-transgenic japonica rice lines with high insect resistance and high yield.They can be used as insect-resistant germplasm materials to overcome the problem of rice yield reduction caused by SSB and reduce the use of pesticides in Northeast China.

Enhanced Vitamin C Production Mediated by an ABA-Induced PTP-like Nucleotidase Improves Plant Drought Tolerance in Arabidopsis and Maize

Abscisic acid(ABA)is a key phytohormone that mediates environmental stress responses.Vitamin C,or L-ascorbic acid(AsA),is the most abundant antioxidant protecting against stress damage in plants.How the ABA and AsA signaling pathways interact in stress responses remains elusive.In this study,we characterized the role of a previously unidentified gene,PTPN(PTP-like Nucleotidase)in plant drought tolerance.In Arabidopsis,(AtPTPN was expressed in multiple tissues and upregulated by ABA and drought treatments.Loss-of-function mutants oiAtPTPN were hyposensitive to ABA but hypersensitive to drought stresses,whereas plants with enhanced expression AtPTPN showed opposite phenotypes to.Overexpression of maize PTPN(ZmPTPN)promoted,while knockdown oiZmPTPN inhibited plant drought tolerance,indicating conserved and positive roles of PTPN in plant drought tolerance.We found that both AtPTPN and ZmPTPN release Pi by hydrolyzing GDP/GMP/dGMP/IMP/dIMP,and that AtPTPN positively regulated AsA production via endogenous Pi content control.Consistently,overexpression of VTC2,the rate-limiting synthetic enzyme in AsA biosynthesis,promoted AsA production and plant drought tolerance,and these effects were largely dependent on AtPTPN activity.Furthermore,we demonstrated that the heat shock transcription factor HSFA6a directly binds the AtPTPN promoter and activates AtPTPN expression.Genetic analyses showed that AtPTPN is required for HSFA6a to regulate ABA and drought responses.Taken together,our data indicate that PTPN-mediated crosstalk between the ABA signaling and AsA biosynthesis pathways positively controls plant drought tolerance.