Abstract

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin and analogs, seeking to highlight the potential of the capuramycin scaffold as a favorable anti-TB therapeutic that warrants further development.

Highlights

  • Tuberculosis (TB), primarily caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb), is one of the oldest and deadliest infectious diseases known to humans

  • Capuramycin-type nucleoside antibiotics, which represent one such possible new class, are natural products that were re-discovered in the early 2000s and have significant promise for drug development as anti-TB

  • This review summarizes the discovery of the capuramycin-type nucleoside antibiotics; progress toward defining their biosynthetic pathway; and synthetic, semisynthetic, and biocatalytic studies aimed at generating analogs with potentially improved therapeutic value

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Summary

Introduction

Tuberculosis (TB), primarily caused by the bacterial pathogen Mycobacterium tuberculosis (Mtb), is one of the oldest and deadliest infectious diseases known to humans. Gram-positive nucleoside-containing natural products have activity as expected, including activity bacteria, Gram-positive such as Streptococcus pneumonia and most species of mycobacteria, Mtb [31]. The shared CarU and 4,5-dehydro-D-manno-pyranuronate of the capuramycin-type nucleoside against Mtb. antibiotics are structural components not found in other natural products [34,35]. The shared and 4,5-dehydro-D-manno-pyranuronate of the capuramycin-type nucleoside antibiotics are structural components not found in other natural products [34,35]. The former is categorized as a high-carbon sugar nucleoside since the furanoside contains six contiguous carbons carbons in place of the D-ribose of the canonical uridine nucleoside. Inhibition of chitin synthase [39]

13 A-102395
Investigation
Identification of the Gene Cluster
Functional Assignment of Gene Products
Biosynthetic
Chemical and Enzymatic Synthesis of Capuramycin and Analogs
Total Synthesis
Preparation of 1 Analogs
Structures
Prospects
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