Post-translational regulation of metabolic checkpoints in plant tetrapyrrole biosynthesis

Tetrapyrrole biosynthesis produces metabolites that are essential for critical reactions in photosynthetic organisms, including chlorophylls, heme, siroheme, phytochromobilins, and their derivatives. Due to the paramount importance of tetrapyrroles, a better understanding of the complex regulation of tetrapyrrole biosynthesis promises to improve plant productivity in the context of global climate change. Tetrapyrrole biosynthesis is known to be controlled at multiple levels-transcriptional, translational and post-translational. This review addresses recent advances in our knowledge of the post-translational regulation of tetrapyrrole biosynthesis and summarizes the regulatory functions of the various auxiliary factors involved. Intriguingly, the post-translational network features three prominent metabolic checkpoints, located at the steps of (i) 5-aminolevulinic acid synthesis (the rate-limiting step in the pathway), (ii) the branchpoint between chlorophyll and heme synthesis, and (iii) the light-dependent enzyme protochlorophyllide oxidoreductase. The regulation of protein stability, enzymatic activity, and the spatial organization of the committed enzymes in these three steps ensures the appropriate flow of metabolites through the tetrapyrrole biosynthesis pathway during photoperiodic growth. In addition, we offer perspectives on currently open questions for future research on tetrapyrrole biosynthesis.