Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers.
Induction of Diverse Cryptic Fungal Metabolites by Steroids and Channel Blockers.
复制标题
DOI：
10.1002/anie.202204519
复制
发表时间：
2022-07-18
影响因子：
16.6
通讯作者：
Seyedsayamdost, Mohammad R.
中科院分区：
文献类型：
--
作者：
Lee, Seoung Rak;Seyedsayamdost, Mohammad R.
真菌提供了天然产品的深层来源，但仍未得到充分利用。可以检测到的大多数生物合成基因簇（BGC）在标准实验室培养物中是沉默的或“隐藏的”，因此它们的产物在常规筛选中不被询问。由于遗传改变是困难的，一些菌株只能在琼脂上生长，我们在此应用了基于琼脂的高通量化学遗传筛选来鉴定真菌BGC的诱导剂。利用R. solani和S.作为测试案例，我们报告了四个化合物组中的13种隐藏代谢物，包括具有新型支架的天然产物硬环素。类固醇是最好的诱导剂，后续研究表明，植物类固醇触发硬环素的合成，这表明对B的抗生素活性。plantarii是S.菌核我们的研究结果为探索真菌-植物相互作用的化学生态学开辟了新的途径，并为发现隐藏的真菌代谢产物提供了一种无遗传学的方法。真菌编码的次级代谢产物种类繁多，有待开发。我们用两种真菌菌株进行了第一次基于琼脂的高通量诱导子筛选，并鉴定了FDA批准的药物作为次级代谢的强增强剂。激发子使13种新型隐蔽代谢物的发现成为可能，特别是具有前所未有的氮杂托烷支架和抗真菌生态竞争对手的抗微生物活性的硬环素。
Fungi offer a deep source of natural products but remain underutilized. Most biosynthetic gene clusters (BGCs) that can be detected are silent or ‘cryptic’ in standard lab cultures and their products are thus not interrogated in routine screens. As genetic alterations are difficult and some strains can only be grown on agar, we have herein applied an agar-based high-throughput chemical genetic screen to identify inducers of fungal BGCs. Using R. solani and S. sclerotiorum as test cases, we report 13 cryptic metabolites in four compound groups, including sclerocyclane, a natural product with a novel scaffold. Steroids were the best elicitors and follow-up studies showed that plant-steroids trigger sclerocyclane synthesis, which shows antibiotic activity against B. plantarii, an ecological competitor of S. sclerotiorum. Our results open new paths to exploring the chemical ecology of fungal-plant interactions and provide a genetics-free approach for uncovering cryptic fungal metabolites. Fungi encode a diverse array of secondary metabolites that remain to be mined. We conducted the first agar-based high-throughput elicitor screen with two fungal strains and identified FDA-approved drugs as strong enhancers of secondary metabolism. The elicitors enabled discovery of 13 novel cryptic metabolites, notably sclerocyclane with an unprecedented azatropane scaffold and antimicrobial activity against an ecological competitor of fungi.
登录
查看更多内容
DOI：
10.1016/j.fgb.2016.01.012
发表时间：
2016-04
期刊：
Fungal genetics and biology : FG & B
影响因子：
--
作者：
Li YF;Tsai KJS;Harvey CJB;Li JJ;Ary BE;Berlew EE;Boehman BL;Findley DM;Friant AG;Gardner CA;Gould MP;Ha JH;Lilley BK;McKinstry EL;Nawal S;Parry RC;Rothchild KW;Silbert SD;Tentilucci MD;Thurston AM;Wai RB;Yoon Y;Aiyar RS;Medema MH;Hillenmeyer ME;Charkoudian LK
通讯作者：
Charkoudian LK
影响因子：
4.8
作者：
Colavolpe, Maria Belen;Villarreal, Natalia Marina;Marina, Maria
通讯作者：
Marina, Maria
影响因子：
9.8
作者：
Hayden, Helen L.;Rochfort, Simone J.;Mele, Pauline M.
通讯作者：
Mele, Pauline M.
影响因子：
7.2
作者：
Griebel, Thomas;Zeier, Juergen
通讯作者：
Zeier, Juergen
影响因子：
14.8
作者：
Bok, Jin Woo;Chiang, Yi-Ming;Szewczyk, Edyta;Reyes-Domingez, Yazmid;Davidson, Ashley D.;Sanchez, James F.;Lo, Hsien-Chun;Watanabe, Kenji;Strauss, Joseph;Oakley, Berl R.;Wang, Clay C. C.;Keller, Nancy P.
通讯作者：
Keller, Nancy P.