Pyrenocine I, a new pyrenocine analog produced by Paecilomyces sp. FKI-3573
Pyrenocine I, a new pyrenocine analog produced by Paecilomyces sp. FKI-3573
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DOI：
10.1038/ja.2010.65
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发表时间：
2010-09-01
影响因子：
3.3
通讯作者：
Omura, Satoshi
中科院分区：
文献类型：
--
作者：
Hashida, Junko;Niitsuma, Megumi;Omura, Satoshi
人类非洲锥虫病，也被称为昏睡病，是由寄生原生动物布氏锥虫的两个亚种引起的。非洲人类锥虫病是撒哈拉以南非洲特有的疾病，在过去的流行病中，它造成了严重和广泛的死亡和发病。世界卫生组织估计，非洲锥虫在2004年造成52000人死亡，预计到2015年将继续下降到36000人（http：//www.cn.org）。dndi。org/）。1目前用于治疗的四种肠胃外药物（苏拉明、喷他脒、依氟鸟氨酸和美拉胂醇）存在重大问题，因为它们毒性高、价格昂贵、难以给药，而且寄生虫对它们的抗药性正在增加。尽管在2009年引入了使用药物的新的组合疗法，但是目前只有一种分子处于用于治疗人类非洲锥虫病的临床开发中（http：//www. dndi。org/）。2因此，迫切需要更有效、更安全、更经济、更易于使用、理想情况下具有新颖作用模式的新型抗锥虫药物。我们的研究小组专注于从微生物代谢产物中筛选抗锥虫药物。3-5我们正在进行的研究发现了一种新的蛋白核菌素，即蛋白核菌素I（1），它是从拟青霉属FKI-3573的培养液中分离出来的，沿着的还有已知的蛋白核菌素A（2）6和B（3）6以及黄绿青霉素（4）（图1）。7所有化合物均具有体外抗锥虫活性。本文报道了它们的发酵、分离、结构鉴定和抗锥虫活性。真菌菌株FKI-3573分离自在美国HI的Hilo收集的土壤样品。FKI-3573的ITS rDNA序列与淡紫拟青霉ATCC 10114（GenBank登录号AY 213665）的匹配率为95.6%。结合形态学特征，初步鉴定FKI-3573为拟青霉属的一个成员。8将菌株FKI-3573的储备培养物接种到100 ml种子培养基中，所述种子培养基由葡萄糖（2.0%）、多肽（0.5%; Nihon Pharmaceutical，Tokyo，Japan）、酵母提取物（0.2%）、KH 2 PO 4（0.1%）、MgSO 4 × 7 H2O（0.05%）和琼脂（0.1%）组成，调节至
Human African trypanosomiasis, also known as sleeping sickness, is caused by two subspecies of the parasitic protozoan, Trypanosoma brucei. Unique to sub-Saharan Africa, human African trypanosomiasis has, in past epidemics, caused significant and widespread mortality and morbidity. The World Health Organization estimated that human African trypanosomiasis caused 52000 deaths in 2004, projecting a continuing fall to a total of 36000 in 2015 (http://www. dndi. org/). 1 There are significant problems with the four parenteral drugs currently used for treatment (suramin, pentamidine, eflornithine and melarsoprol) as they are highly toxic, expensive, difficult to administer, and parasite resistance to them is increasing. Although a new combination therapy using drugs was introduced in 2009, only one molecule is currently in clinical development for treatment of human African trypanosomiasis (http://www. dndi. org/). 2 Therefore, there is an urgent need for new antitrypanosomal drugs that are more effective, safer, affordable easier to use and which, ideally, have a novel mode of action.Our research group has focused on the screening of antitrypanosomal agents from microbial metabolites. 3–5 Our ongoing studies have led to the discovery of a novel pyrenocine, pyrenocine I (1), which was isolated from the culture broth of Paecilomyces sp. FKI-3573, along with the known pyrenocines A (2) 6 and B (3) 6 and citreoviridin (4)(Figure 1). 7 All of the compounds exhibit in vitro antitrypanosomal activity. In this article, we report their fermentation, isolation, structure elucidation and antitrypanosomal activity. Fungal strain FKI-3573 was isolated from a soil sample collected in Hilo, HI, USA. The ITS rDNA sequence of FKI-3573 was a 95.6% match to Paecilomyces lilacinus ATCC 10114 (GenBank accession number AY213665). From this information, combined with morphological characteristics, FKI-3573 was identified to be a member of the Paecilomyces genus. 8 A stock culture of strain FKI-3573 was inoculated into 100 ml of seed medium, consisting of glucose (2.0%), Polypepton (0.5%; Nihon Pharmaceutical, Tokyo, Japan), yeast extract (0.2%), KH2PO4 (0.1%), MgSO4Á7H2O (0.05%) and agar (0.1%), adjusted to