Diverse enzymatic chemistry for propionate side chain cleavages in tetrapyrrole biosynthesis

Tetrapyrroles represent a unique class of natural products that possess diverse chemical architectures and exhibit a broad range of biological functions. Accordingly, they attract keen attention from the natural product community. Many metal-chelating tetrapyrroles serve as enzyme cofactors essential for life, while certain organisms produce metal-free porphyrin metabolites with biological activities potentially beneficial for the producing organisms and for human use. The unique properties of tetrapyrrole natural products derive from their extensively modified and highly conjugated macrocyclic core structures. Most of these various tetrapyrrole natural products biosynthetically originate from a branching point precursor, uroporphyrinogen III, which contains propionate and acetate side chains on its macrocycle. Over the past few decades, many modification enzymes with unique catalytic activities, and the diverse enzymatic chemistries employed to cleave the propionate side chains from the macrocycles, have been identified. In this review, we highlight the tetrapyrrole biosynthetic enzymes required for the propionate side chain removal processes and discuss their various chemical mechanisms.One-Sentence Summary This mini-review describes various enzymes involved in the propionate side chain cleavages during the biosynthesis of tetrapyrrole cofactors and secondary metabolites. Graphical Abstract

Automated summary

Tetrapyrroles are a unique class of natural products with diverse chemical structures and broad biological functions. They play essential roles as enzyme cofactors and certain metal-free porphyrin metabolites may have beneficial activities for both organisms and humans. The unique properties of tetrapyrrole natural products come from their extensively modified and conjugated macrocyclic core structures. The biosynthesis of most tetrapyrroles starts from a precursor molecule called uroporphyrinogen III, which contains propionate and acetate side chains. Several modification enzymes and catalytic activities have been identified for cleavage of the propionate side chains from the macrocycles.