Asymmetric Alkene and Arene Halofunctionalization Reactions in Meroterpenoid Biosynthesis
TLDR
A group of vanadium-dependent chloroperoxidase enzymes that catalyze halogen-assisted cyclization and rearrangement reactions and have inspired biomimetic syntheses of numerous meroterpenoid natural products are discovered and characterized.Abstract:
Meroterpenoid natural products are important bioactive molecules with broad distribution throughout nature. In Streptomyces bacteria, naphthoquinone-based meroterpenoids comprise a simple yet structurally fascinating group of natural product antibiotics that are enzymatically constructed through a series of asymmetric alkene and arene halofunctionalization reactions. This account article highlights our discovery and characterization of a group of vanadium-dependent chloroperoxidase enzymes that catalyze halogen-assisted cyclization and rearrangement reactions and have inspired biomimetic syntheses of numerous meroterpenoid natural products. 1 Introduction 2 Early Biosynthetic Insights and the Characterization of Alkene Halofunctionalization in Napyradiomycin Biosynthesis 3 Discovery of the Merochlorin Natural Products and Enzymatic Aryl Halofunctionalization 4 Discovery and Development of Unifying THN-Based Meroterpenoid Biosynthesis and Synthesis Approaches 5 Insights into Naphterpin and Marinone Biosynthesis Involving Cryptic Aryl Halofunctionalization Reactions 6 Closing Thoughtsread more
Citations
More filters
Journal ArticleDOI
Enzymatic Cascade Reactions in Biosynthesis.
TL;DR: Four types of enzymatic cascade reactions are discussed: those involving nucleophilic, electrophilic, pericyclic, and radical reactions, and two subtypes of enzymes that generate radical cascades exist at opposite ends of the oxygen abundance spectrum.
Journal ArticleDOI
Terpene synthases in disguise: enzymology, structure, and opportunities of non-canonical terpene synthases.
TL;DR: 12 families of non-canonical TSs are identified and examined, providing immense opportunities to understand how nature evolved different tools for terpene biosynthesis by structural and mechanistic characterization while affording new probes for the discovery of novel terpenoid natural products and gene clusters via genome mining.
Journal ArticleDOI
Meroterpenoid natural products from Streptomyces bacteria – the evolution of chemoenzymatic syntheses
Lauren A. M. Murray,Shaun M. K. McKinnie,Bradley S. Moore,Bradley S. Moore,Jonathan H. George +4 more
TL;DR: The application of genome mining techniques to marine Streptomyces bacteria led to the discovery of unique prenyltransferase and vanadium-dependent haloperoxidase enzymes that can be used as highly selective biocatalysts in fully enzymatic total syntheses, thus overcoming the limitations of purely chemical reagents.
Journal ArticleDOI
Catalytic Asymmetric Construction of Halogenated Stereogenic Carbon Centers by Direct Vinylogous Mannich-Type Reaction
TL;DR: The utility of present methodology was demonstrated by the asymmetric synthesis of a common intermediate toward the synthesis of two chiral 2,3-disubstituted piperidine pharmaceuticals.
Journal ArticleDOI
Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products
Lauren A. M. Murray,Shaun M. K. McKinnie,Shaun M. K. McKinnie,Henry P. Pepper,Reto Erni,Reto Erni,Zachary D. Miles,Zachary D. Miles,Michelle C. Cruickshank,Borja López-Pérez,Bradley S. Moore,Bradley S. Moore,Jonathan H. George +12 more
TL;DR: It is proposed that cryptic halogenation of THN derivatives by vanadium-dependent chloroperoxidase (VCPO) enzymes is key to this biosynthetic pathway, despite the absence of chlorine in these natural products.
References
More filters
Journal ArticleDOI
Natural Products Version 2.0: Connecting Genes to Molecules
TL;DR: This Perspective explores how connecting Nature's small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and non-ribosomal peptides.
Journal ArticleDOI
Diversity of the biosynthesis of the isoprene units
Tomohisa Kuzuyama,Haruo Seto +1 more
TL;DR: This review covers the biosynthesis of the starter units of terpenoids via the nonmevalonate pathway together with a new enzyme involved in the conversion of IPP and DMAPP, i.e type 2 IPP isomerase.
Journal ArticleDOI
Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products
TL;DR: These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases.
Journal ArticleDOI
Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse
Vinayak Agarwal,Zachary D. Miles,Jaclyn M. Winter,Alessandra S. Eustáquio,Abrahim El Gamal,Bradley S. Moore +5 more
TL;DR: The scope and mechanism of nature's halogenation and dehalogenation enzymatic strategies are detailed, gaps in understanding are highlighted, and where new advances in the field might arise in the near future are posits.
Journal ArticleDOI
Exploring the chemistry and biology of vanadium-dependent haloperoxidases.
TL;DR: The chemistry and biology of vanadium-dependent haloperoxidases from fungi and marine algae and the emergence of new bacterial members that extend the biological function of these poorly understood halogenating enzymes are highlighted.