Origins and structure of chloroplastic and mitochondrial plant protoporphyrinogen oxidases: implications for the evolution of herbicide resistance

Abstract

Protoporphyrinogen IX oxidase (PPO)-inhibiting herbicides are effective tools to control a broad spectrum of weeds, including those that have evolved resistance to glyphosate. Their utility is being threatened by the appearance of biotypes that are resistant to PPO inhibitors. While the chloroplastic PPO1 isoform is thought to be the primary target of PPO herbicides, evolved resistance mechanisms elucidated to date are associated with changes to the mitochondrial PPO2 isoform, suggesting that the importance of PPO2 has been underestimated. Our investigation of the evolutionary and structural biology of plant PPOs provides some insight into the potential reasons why PPO2 is the preferred target for evolution of resistance. The most common target-site mutation imparting resistance involved the deletion of a key glycine codon. The genetic environment that facilitates this deletion is apparently only present in the gene encoding PPO2 in a few species. Additionally, both species with this mutation (Amaranthus tuberculatus and Amaranthus palmeri) have dual targeting of PPO2 to both the chloroplast and the mitochondria, which might be a prerequisite to impart herbicide resistance. The most recent target-site mutations have substituted a key arginine residue involved in stabilizing the substrate in the catalytic domain of PPO2. This arginine is highly conserved across all plant PPOs, suggesting that its substitution could be equally likely on PPO1 and PPO2, yet it has only occurred on PPO2, underscoring the importance of this isoform for the evolution of herbicide resistance. © 2017 Society of Chemical Industry.

A novel mutation A212T in chloroplast Protoporphyrinogen oxidase (PPO1) confers resistance to PPO inhibitor Oxadiazon in Eleusine indica

“…In our opinion, questions remain regarding single or dual inhibition of chloroplast‐targeted PPO1 and mitochondrial‐targeted PPO2 by PPO inhibitors. In Amaranthus species, the PPO2 is dual targeted to chloroplast and mitochondria, which suggests that the current mutations reported in PPO2 can protect PPO activity not only in the mitochondria, but also in the chloroplast . Nonetheless, the computational modeling of previously reported mutation sites in PPO2 and our novel mutation A212T in PPO1 suggest the hypothesis that not all PPO‐inhibiting herbicides act the same (at the same site of action or with the same affinity) and some PPO‐inhibiting herbicides that may have preferences for one or the other target isoform are worthy of future exploration.…”

“…34 This enlargement of the substrate binding pocket reduces the affinity of PPO inhibitors for PPO2. The substitution R128L in PPO2 caused cross-resistance because R128 is in the pocket between the substrate entryway and the herbicide active site, 21,[35][36][37] which is essential for stabilizing the substrate in the catalytic domain. Computational modeling indicated that the mutation of R128G removed the important hydrogen-bonding interactions with acifluorfen and sulfentrazone, reducing the binding of these PPO inhibitors.…”

Editorial

“…Weed resistance to protoporphyrinogen oxidase-inhibiting and auxinic herbicides was reviewed. 11,12 Reviews also provided an ecological perspective on managing weeds during selection for herbicide resistance 13 and on harvesting and destroying weed seeds to manage weeds. 14 A later issue of the journal had a review on improving management of weed seeds in soil.…”

Coevolution of resistance to PPO inhibitors in waterhemp (Amaranthus tuberculatus) and Palmer amaranth (Amaranthus palmeri)

“…PPX1 and PPX2 are two different nuclear genes that encode two isoforms of PPO; PPO1 is targeted to plastids, and PPO2 is targeted to mitochondria (Lermontova et al 1997). In at least some species, the enzyme encoded by PPX2 is dual targeted to both plastids and mitochondria (Dayan et al 2018). Thus, a mutation in this gene can result in target-site resistance in both organelles (Patzoldt et al 2006).…”