Isolation, Structure, and Antibacterial Activities of Lucensimycins D−G, Discovered from Streptomyces lucensis MA7349 Using an Antisense Strategy

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• 作者：Sheo B. Singh ; Deborah L. Zink ; Karen Dorso ; Mary Motyl ; Oscar Salazar ; Angela Basilio ; Francisca Vicente ; Kevin M. Byrne ; Sookhee Ha ; Olga Genilloud
• 刊名：Journal of Natural Products
• 出版年：2009
• 出版时间：March 27, 2009
• 年：2009
• 卷：72
• 期：3
• 页码：345-352
• 全文大小：208K
• 年卷期：v.72,no.3(March 27, 2009)
• ISSN：1520-6025

文摘

Bacterial resistance to existing antibiotics continues to grow, necessitating the discovery of new compounds of this type. Antisense-based whole-cell target-based screening is a new and highly sensitive antibiotic discovery approach that has led to a number of new natural product antibiotics. Screening with a rpsD-sensitized strain led to the discovery of a number of natural product polyketides from Streptomyces lucensis. Complete workup of the fermentation extract of this strain allowed for the isolation of seven new compounds, lucensimycins A−G (1−3, 4a, 5−7), with varying degrees of antibacterial activities. Lucensimycin E (5) exhibited the best activity and showed MIC values of 32 μg/mL against Staphylococcus aureus and 8 μg/mL against Streptococcus pneumoniae. The isolation, structure elucidation, and antibacterial activities of four new members, lucensimycins D−G, are described. Lucensimycins D (4a) and E (5) are N-acetyl-l-cysteine adducts of lucensimycin A (1). Semisynthesis of lucensimycins D and E from lucensimycin A has also been described. Lucensimycins F and G are myo-inositolyl-α-2-amino-2-deoxy-l-idosyl amide derivatives of lucensimycins D and E, respectively. The relative configuration of these compounds was determined, in part, by molecular dynamics simulations.