Novel Action Targets of Natural Product Gliotoxin in Photosynthetic Apparatus

Abstract

Gliotoxin (GT) is a fungal secondary metabolite that has attracted great interest due to its high biological activity since it was discovered by the 1930s. It exhibits a unique structure that contains a N-C = O group as the characteristics of the classical PSII inhibitor. However, GT's phytotoxicity, herbicidal activity and primary action targets in plants remain hidden. Here, it is found that GT can cause brown or white leaf spot of various monocotyledonous and dicotyledonous plants, being regarded as a potential herbicidal agent. The multiple sites of GT action are located in two photosystems. GT decreases the rate of oxygen evolution of PSII with an I 50 value of 60 µM. Chlorophyll fluorescence data from Chlamydomonas reinhardtii cells and spinach thylakoids implicate that GT affects both PSII electron transport at the acceptor side and the reduction rate of PSI end electron acceptors' pool. The major direct action target of GT is the plastoquinone Q B-site of the D1 protein in PSII, where GT inserts in the Q B binding niche by replacing native plastoquinone (PQ) and then interrupts electron flow beyond plastoquinone Q A. This leads to severe inactivation of PSII RCs and a significant decrease of PSII overall photosynthetic activity. Based on the simulated modeling of GT docking to the D1 protein of spinach, it is proposed that GT binds to the-Q B-site through two hydrogen bonds between GT and D1-Ser264 and D1-His252. A hydrogen bond is formed between the aromatic hydroxyl oxygen of GT and the residue Ser264 in the D1 protein. The 4-carbonyl group of GT provides another hydrogen bond to the residue D1-His252. So, it is concluded that GT is a novel natural PSII inhibitor. In the future, GT may have the potential for development into a bioherbicide or being utilized as a lead compound to design more new derivatives.

Rational Design, Synthesis and Evaluation of Indole Nitrogen Hybrids as Photosystem II Inhibitors

“…In addition, herbicides that inhibit PSII prefer the position near the loop made by Ser264 and Phe265 at protein D1. The same orientation for indole derivatives and DCMU in the binding site was observed (57)(58)(59). Figure 7 exhibits the best docking pose of compounds 15a and 15b including hydrogen-bonding interactions, with binding energies of À8.47 kcalmol À1 and À7.39 kcalmol À1 , respectively.…”

Imaging of Chlorophyll a Fluorescence in Natural Compound-Induced Stress Detection

“…CFI has been used also to evaluate the phytotoxic effects of natural compounds produced by fungi and bacteria. Guo et al (2019) demonstrated that gliotoxin, a fungal secondary metabolite, affects both the electron transport through PSII at the acceptor side and the reduction rate of PSI end electron acceptors’ pool. Through CFI, authors identified the concentration inducing physical damage to PSII.…”

The hydrophobicity of mutations targeting D1:Val219 modifies formate and diuron binding in the quinone‐Fe‐acceptor complex of Photosystem II

“…While there are currently no X‐ray‐derived PS II structures with DCMU bound, computational modeling has predicted the position of DCMU bound in PS II (Guo et al . 2020). Based on these predictions, DCMU is estimated to be bound approximately 5.5 Å from the Val219 residue (Figure 6A).…”

“…(A) Hypothesized binding position of DCMU based on calculations from Guo et al . (2020). (B) Hypothesized binding position of formate based on the position of the bicarbonate ligand to the nonheme iron.…”

“…DCMU binds in the Q B -binding pocket; therefore, the altered sensitivity to DCMU in our V219I mutant provides further evidence that binding at the Q B -binding pocket is altered. While there are currently no X-ray-derived PS II structures with DCMU bound, computational modeling has predicted the position of DCMU bound in PS II (Guo et al 2020). Based on these predictions, DCMU is estimated to be bound approximately 5.5 Å from the Val219 residue (Figure 6A).…”