Thiazomycins, Thiazolyl Peptide Antibiotics from Amycolatopsis fastidiosa

• Published in: Journal of natural products (Washington, D.C.) Vol. 72; no. 5; pp. 841 - 847
• Main Authors: Zhang, Chaowei, Herath, Kithsiri, Jayasuriya, Hiranthi, Ondeyka, John G, Zink, Deborah L, Occi, James, Birdsall, Gwyneth, Venugopal, Jayashree, Ushio, Misti, Burgess, Bruce, Masurekar, Prakash, Barrett, John F, Singh, Sheo B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 22.05.2009; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Actinomycetales - chemistry; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Applied microbiology; Biological and medical sciences; Chemistry, Medicinal; Combinatorial Chemistry Techniques; Fundamental and applied biological sciences. Psychology; Life Sciences & Biomedicine; Microbial Sensitivity Tests; Microbiology; Molecular Structure; Peptides - chemistry; Peptides - isolation & purification; Peptides - pharmacology; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; Stereoisomerism; Thiazoles - chemistry; Thiazoles - isolation & purification; Thiazoles - pharmacology; NOCATHIACIN-I ANALOGS; GLYCOTHIOHEXIDE-ALPHA; DEHYDROALANINE; SEBEKIA SP; ANTIBACTERIAL ACTIVITY; CONVERSION; BIOSYNTHESIS; PLATENSIMYCIN; INHIBITOR; FABF; Peptides; Thiazole derivatives; Amycolatopsis; Biosynthesis; Pseudonocardiaceae; Biological activity; Macrocycle; Antibiotic; Microbial origin; Bacteria; Isolation; Actinomycetes; Antibacterial agent; Structural analysis
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np800783b

Thiazolyl peptides are a class of highly rigid trimacrocyclic compounds consisting of varying but large numbers of thiazole rings. The need for new antibacterial agents to treat infections caused by resistant bacteria prompted a reinvestigation of this class, leading to the previous isolation of thiazolyl peptides, namely, thiazomycin (5) and thiazomycin A (6), congeners of nocathiacins (1−4). Continued chemical screening led to the isolation of six new thiazolyl peptide congeners (8−13), of which three had truncated structures lacking an indole residue. From these, compound 8 showed activity similar to thiazomycin. Two compounds (9 and 10) showed intermediate activities, and the three truncated compounds (11−13) were essentially inactive. The discovery of the truncated compounds revealed the minimal structural requirements for activity and suggested probable biosynthetic pathways for more advanced compounds. The isolation, structure elucidation, antibacterial activity, and proposed biogenesis of thiazomycins are herein described.