Spirohexalines, new inhibitors of bacterial undecaprenyl pyrophosphate synthase, produced by Penicillium brasilianum FKI-3368
Spirohexalines, new inhibitors of bacterial undecaprenyl pyrophosphate synthase, produced by Penicillium brasilianum FKI-3368
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DOI：
10.1038/ja.2012.83
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Tomoda, Hiroshi
中科院分区：
文献类型：
--
作者：
Inokoshi, Junji;Nakamura, Yuichiro;Tomoda, Hiroshi
对细菌十一异戊二烯焦磷酸 (UPP) 合酶进行酶测定，以筛选微生物培养液中 UPP 合酶的抑制剂。在此筛选计划过程中，发现巴西青霉 FKI-3368 水稻培养物的乙醇提取物可抑制 UPP 合酶活性。通过活性引导纯化，通过乙酸乙酯萃取硅胶和十八烷基硅烷柱色谱以及高效液相色谱，分离出一种新的化合物螺己环，以及结构相关且已知的绿藻毒素。通过光谱分析（包括 NMR）阐明了螺环己啉的结构。螺己环素和绿毛毒素具有共同的六环素结构，由四环素型环与螺型环融合产生。它们抑制 UPP 合酶活性，IC50 值分别为 9.0 和 4.0 muM。抗生素杂志 (2013) 66, 37-41; doi：10.1038/ja.2012.83； 2012 年 11 月 21 日在线发布
An enzyme assay for bacterial undecaprenyl pyrophosphate (UPP) synthase was performed to screen microbial culture broths for inhibitors of UPP synthase. During the course of this screening program, an EtOH extract of a rice culture of Penicillium brasilianum FKI-3368 was found to inhibit UPP synthase activity. From activity-guided purification, a new compound-designated spirohexaline was isolated together with the structurally related and known viridicatumtoxin by ethyl acetate extraction silica gel and octadecylsilane column chromatographies and high-performance liquid chromatography. The structure of spirohexaline was elucidated by spectroscopic analysis, including NMR. Spirohexaline and viridicatumtoxin have a common hexacycline structure produced by fusion of a tetracycline-type ring with a spiro-type ring. They inhibited UPP synthase activity with IC50 values of 9.0 and 4.0 mu M, respectively. The Journal of Antibiotics (2013) 66, 37-41; doi: 10.1038/ja.2012.83; published online 21 November 2012