Department of Natural products-Biology, Piramal Enterprises Limited, Mumbai, India.
Lett Appl Microbiol. 2014 Jun;58(6):591-6. doi: 10.1111/lam.12229. Epub 2014 Mar 11.
A new polyene macrolide antibiotic PN00053 was isolated from the fermentation broth of Streptomyces sp. wild-type strain MTCC-5680. The producer strain was isolated from fertile mountain soil of Naldehra region, Himachal Pradesh, India. The compound PN00053 was purified through various steps of chromatographic techniques and bio-activity guided fractionation followed by its characterization using physiochemical properties, spectral data ((1) H-NMR, (13) C-NMR, HMBC, HSQC, and COSY) and MS analysis. PN00053 exhibited broad spectrum in vitro antifungal activity against strains of Aspergillus fumigatus (HMR), A. fumigatus ATCC 16424, Candida albicans (I.V.), C. albicans ATCC 14503, C. krusei GO6, C. glabrata HO4, Cryptococcus neoformans, Trichophyton sp. as well as fluconazole resistant strains C. krusei GO3 and C. glabrata HO5. It did not inhibit growth of gram positive and gram-negative bacteria, displaying its specificity against fungi.
PN00053 is a novel polyene macrolide isolated from a wild strain of Streptomyces sp. PM0727240 (MTCC5680), an isolate from the mountainous rocky regions of Himachal Pradesh, India. The compound is a new derivative of the antibiotic Roflamycoin [32, 33-didehydroroflamycoin (DDHR)]. It displayed broad spectrum antifungal activity against yeast and filamentous fungi. However, it did not show any antibacterial activity. The in vitro study revealed that PN00053 has better potency as compared to clinical gold standard fluconazole. The development of pathogenic resistance against the polyenes has been seldom reported. Hence, we envisage PN00053 could be a potential antifungal lead.
一种新型多烯大环内酯抗生素 PN00053 从野生型链霉菌 MTCC-5680 的发酵液中分离得到。该生产菌株是从印度喜马偕尔邦纳德赫拉地区肥沃的山地土壤中分离出来的。化合物 PN00053 通过各种色谱技术和生物活性导向的分步纯化，以及使用物理化学性质、光谱数据（（1）H-NMR、（13）C-NMR、HMBC、HSQC 和 COSY）和 MS 分析进行其表征。PN00053 表现出广谱的体外抗真菌活性，对烟曲霉（HMR）、烟曲霉 ATCC 16424、白色念珠菌（I.V.）、白色念珠菌 ATCC 14503、克柔念珠菌 GO6、光滑念珠菌 HO4、新型隐球菌、毛癣菌以及氟康唑耐药菌株克柔念珠菌 GO3 和光滑念珠菌 HO5 的菌株均有抑制作用。它不抑制革兰氏阳性和革兰氏阴性细菌的生长，显示出对真菌的特异性。
PN00053 是一种从链霉菌野生株 PM0727240（MTCC5680）中分离得到的新型多烯大环内酯抗生素，该野生株是从印度喜马偕尔邦多山多石的地区分离得到的。该化合物是抗生素罗氟霉素的新衍生物[32,33-二脱氢罗氟霉素（DDHR）]。它对酵母和丝状真菌表现出广谱的抗真菌活性。然而，它没有显示出任何抗菌活性。体外研究表明，PN00053 的活性优于临床金标准氟康唑。多烯类药物的致病性耐药性发展很少有报道。因此，我们预计 PN00053 可能是一种有潜力的抗真菌先导化合物。
