Peculiarities of meroterpenoids and their bioproduction.

Meroterpenoids are a class of terpenoid-containing hybrid natural products with impressive structural architectures and remarkable pharmacological activities. Remarkable advances in enzymology and synthetic biology have greatly contributed to the elucidation of the molecular basis for their biosynthesis. Here, we review structurally unique meroterpenoids catalyzed by novel enzymes and unusual enzymatic reactions over the period of last 5 years. We also discuss recent progress on the biomimetic synthesis of chrome meroterpenoids and synthetic biology-driven biomanufacturing of tropolone sesquiterpenoids, merochlorins, and plant-derived meroterpenoid cannabinoids. In particular, we focus on the novel enzymes involved in the biosynthesis of polyketide-terpenoids, nonribosomal peptide-terpenoids, terpenoid alkaloids, and meroterpenoid with unique structures. The biological activities of these meroterpenoids are also discussed. The information reviewed here might provide useful clues and lay the foundation for developing new meroterpenoid-derived drugs. KEY POINTS: • Meroterpenoids possess intriguing structural features and relevant biological activities. • Novel enzymes are involved in the biosynthesis of meroterpenoids with unique structures. • Biomimetic synthesis and synthetic biology enable the construction and manufacturing of complex meroterpenoids.