Cryptic Biosynthesis of the Berkeleypenostatins from Coculture of Extremophilic Penicillium sp.

Cryptic Biosynthesis of the Berkeleypenostatins from Coculture of Extremophilic Penicillium sp.
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DOI:
10.1021/acs.jnatprod.1c00248
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发表时间:
2021-05-28
影响因子:
5.1
通讯作者:
Apedaile L
Apedaile L
中科院分区:
生物学2区
文献类型:
--
作者:
Stierle AA;Stierle DB;Decato D;Alverson J;Apedaile L

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褐色青霉和卡门伯蒂青霉/棒曲霉的共培养发酵产生了berkeleypenostatins A-G(1-7)以及先前报道的berkeleylactones A-H、已知的大环内酯A26771 B、桔霉素和展青霉素。与berkeleylactones一样,在两种纯培养物中均没有berkeleypenostatin的证据。根据光谱数据推断了化合物的结构,并通过单晶X-射线晶体学确定了Berkeleypenostatin A(1)的绝对构型。Berkeleypenostatin A(1)和E(5)抑制人胰腺癌细胞(HPAF-Ⅱ)的迁移。这两种化合物都由NCI开发治疗计划进行了测试。在NCI 60细胞五剂量筛选中,Berkeleypenostatin E(5)是两种中活性更高的,对所有白血病细胞系以及大多数结肠癌、CNS、黑色素瘤、卵巢癌、前列腺癌、肾癌和乳腺癌细胞系的总生长抑制(TGI)为1-10 μM。
Coculture fermentation of Penicillium fuscum and P. camembertii/clavigerum yielded berkeleypenostatins A-G (1–7) as well as the previously reported berkeleylactones A-H, the known macrolide A26771B, citrinin and patulin. As was true with the berkeleylactones, there was no evidence of the berkeleypenostatins in either axenic culture. The structures were deduced from analyses of spectral data, and the absolute configuration of berkeleypenostatin A (1) was determined by single crystal X-ray crystallography. Berkeleypenostatin A (1) and E (5) inhibited migration of human pancreatic carcinoma cells (HPAF-II). Both compounds were tested by the NCI Developmental Therapeutics Program. In the NCI 60 Cell Five-Dose Screen, Berkeleypenostatin E (5) was the more active of the two, with 1–10 μM total growth inhibition (TGI) of all leukemia cell lines, as well as the majority of colon, CNS, melanoma, ovarian, prostate, renal, and breast cancer cell lines.
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