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Research Project: Novel Weed Management Tools from Natural Product-Based Discoveries

Location: Natural Products Utilization Research

Title: Spliceostatin C, a component of a microbial bioherbicide, is a potent phytotoxin that inhibits the spliceosome

item Bajsa-Hirschel, Joanna
item Pan, Zhiqiang - Peter
item PADNEY, PANKAJ - University Of Mississippi
item ASOLKAR, RATNAKAR - Bioceres Crop Solutions
item GOPAL CHITTIBOYINA, AMAR - University Of Mississippi
item BODDY, LOUIS - Bioceres Crop Solutions
item MACHINGURA, MARYLOU - Georgia Southern University
item DUKE, STEPHEN - University Of Mississippi

Submitted to: Frontiers in Plant Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/7/2022
Publication Date: 1/12/2023
Citation: Bajsa Hirschel, J.N., Pan, Z., Padney, P., Asolkar, R., Gopal Chittiboyina, A., Boddy, L., Machingura, M., Duke, S.O. 2023. Spliceostatin C, a component of a microbial bioherbicide, is a potent phytotoxin that inhibits the spliceosome. Frontiers in Plant Science.

Interpretive Summary: Among factors which significantly endanger crops and effect yields are herbicide-resistant weed populations. Development of a bioherbicide with a new mode of action (MoA) would provide a needed alternative for managing resistant weeds. The main goal of this study was to investigate and confirm the MoA of a phytotoxic compound called spliceostatin C (SPC) which originated from the soil bacterium Bulkholderia spp. Our results prove that spliceostatin C inhibits splicing. SPC, along with romidepsin, is a component of a bioherbicide that is under development. A bioherbicide with two active ingredients, each with a novel mode of action (inhibition of histone deacetylase and spliceosome function), would make it very difficult for target weeds to evolve either target site or non-target site resistance. There are no weed management products on the market with such attributes.

Technical Abstract: Spliceostatin C (SPC) is a component of a bioherbicide isolated from the soil bacterium Burkholderia rinojensis. The chemical structure of SPC closely resembles spliceostatin A (SPA) which was characterized as an anticancer agent and splicing inhibitor. SPC inhibited the growth of Arabidopsis thaliana seedlings with an IC50 value of 2.2 µM. The seedlings exposed to SPC displayed a significant response with decreased root length and number and inhibition of gravitropism. Reverse transcriptase semi-quantitative PCR (RT-sqPCR) analyses of 19 selected genes demonstrated the active impact of SPC on the quality and quantity of transcripts that underwent intron rearrangements such as intron retention and alternative 5’ or 3’ splicing site as well as up or down expression upon exposure to SPC. Qualitative and quantitative proteomic profiles identified 66 proteins that were significantly affected by SPC treatment. Further proteomics data analysis revealed that spliceostatin C induces hormone-related responses in Arabidopsis seedlings. In silico binding studies showed that SPC binds to a pocket between the SF3B3 and PF5A of the spliceosome.