Biosynthesis and Chemical Synthesis of Albomycin Nucleoside Antibiotics.
Meiyan WangYuxin ZhangLanxin LvDekun KongGuoqing NiuPublished in: Antibiotics (Basel, Switzerland) (2022)
The widespread emergence of antibiotic-resistant bacteria highlights the urgent need for new antimicrobial agents. Albomycins are a group of naturally occurring sideromycins with a thionucleoside antibiotic conjugated to a ferrichrome-type siderophore. The siderophore moiety serves as a vehicle to deliver albomycins into bacterial cells via a "Trojan horse" strategy. Albomycins function as specific inhibitors of seryl-tRNA synthetases and exhibit potent antimicrobial activities against both Gram-negative and Gram-positive bacteria, including many clinical pathogens. These distinctive features make albomycins promising drug candidates for the treatment of various bacterial infections, especially those caused by multidrug-resistant pathogens. We herein summarize findings on the discovery and structure elucidation, mechanism of action, biosynthesis and immunity, and chemical synthesis of albomcyins, with special focus on recent advances in the biosynthesis and chemical synthesis over the past decade (2012-2022). A thorough understanding of the biosynthetic pathway provides the basis for pathway engineering and combinatorial biosynthesis to create new albomycin analogues. Chemical synthesis of natural congeners and their synthetic analogues will be useful for systematic structure-activity relationship (SAR) studies, and thereby assist the design of novel albomycin-derived antimicrobial agents.
Keyphrases
- gram negative
- multidrug resistant
- structure activity relationship
- drug resistant
- staphylococcus aureus
- acinetobacter baumannii
- cell wall
- klebsiella pneumoniae
- induced apoptosis
- small molecule
- emergency department
- antimicrobial resistance
- combination therapy
- high throughput
- replacement therapy
- cell proliferation
- pseudomonas aeruginosa
- cell cycle arrest
- anti inflammatory