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Inhibitors of lysine biosynthesis enzymes as potential new herbicides

Emily Mackie, Mirrin McKay, Andrew Barrow, Tatiana Soares da Costa

Abstract

Lysine is an amino acid that is essential for the growth and development of all organisms owing to its role in a plethora of critical biological functions and reactions. In plants, lysine is synthesised via five sequential enzyme-catalysed reactions collectively known as the diaminopimelate (DAP) pathway, whereas animals are reliant on their plant dietary intake to obtain lysine. Given that lysine is one of the most nutritionally limiting amino acids, several studies have focused on developing strategies to modulate the activity of DAP pathway enzymes to improve the nutritional value of crops. More recently, research has emerged on the potential of inhibiting DAP pathway enzymes for the development of herbicides with a novel mode of action. An overreliance on a small number of modes of action has led to a herbicide resistance crisis, necessitating the development of new modes of action to which no resistance exists. As such, the first herbicidal inhibitors of the DAP pathway have been developed, which target the first three enzymes in lysine biosynthesis. This review explores the structure, function and inhibition of these enzymes, as well as highlighting promising avenues for the future development of new plant lysine biosynthesis inhibitors.

FP25030  Accepted 28 April 2025

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