Peculiarities of meroterpenoids and their bioproduction

Abstract

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 five 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.

Total Synthesis of Natural Products using Gold Catalysis

“…Merochlorin A belongs to the class of meroterpenoids [92] . It was extracted from a marine‐based actinomycete strain CNH189 obtained from the ocean coast near Oceanside, California [93,94] .…”

“…Merochlorin A belongs to the class of meroterpenoids. [92] It was extracted from a marine-based actinomycete strain CNH189 obtained from the ocean coast near Oceanside, California. [93,94] Merochlorin A is an intricate natural product having an extremely packed tetracyclic bicycle[3.2.1]octadione skeleton.…”

A Fungal Promiscuous UbiA Prenyltransferase Expands the Structural Diversity of Chrodrimanin-Type Meroterpenoids

“…The biosynthesis of meroterpenoids basically involves the combination of an isoprenoid with other pathways such as polyketide (PK), nonribosomal peptide (NRP), and shikimate, where prenyltransferases (PTases) play a pivotal role in building up the hybrid isoprenoid skeletons by attaching the appropriate terpene parts to their nonterpenoid acceptors (Figure S1). ,,, UbiA-type PTases represent a family of membrane-embedded PTases that generally catalyze the Mg 2+ -dependent transfer of a hydrophobic polyprenyl chain such as dimethylallyl pyrophosphate (DMAPP), geranylgeranyl diphosphate (GPP), farnesyl pyrophosphate (FPP), or geranylgeranyl pyrophosphate (GGPP) onto aromatic acceptor molecules. − This group of PTases is involved in the biosynthesis of a variety of small molecules including as dolichols, ubiquinones, hemes, plant chlorophylls, vitamins E and K, and structural lipids, in addition to fungal meroterpenoids …”

Total Synthesis of Atrachinenins A and B

“…Their existence can therefore inspire the development of spectacular sequences of predisposed transformations and the discovery of novel modes of chemical reactivity . For example, atrachinenins A–C ( 1 – 3 , Figure ) are a family of structurally intricate but racemic meroterpenoid natural products recently isolated from the rhizomes of Atractylodes chinesis, a plant widely used in traditional Chinese medicine. The most complex member of the family, atrachinenin B ( 2 ), features a cage-like pentacyclic ring system with seven contiguous stereocenters and a peroxyhemiacetal bridge.…”