Overexpression of transcriptional regulator and tailoring enzyme leads to the discovery of anti-inflammatory meroterpenoids from marine-derived fungus Alternaria alternata JJY-32
Overexpression of transcriptional regulator and tailoring enzyme leads to the discovery of anti-inflammatory meroterpenoids from marine-derived fungus Alternaria alternata JJY-32
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DOI：
10.3389/fmars.2022.1015684
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发表时间：
2022-10
期刊：
影响因子：
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通讯作者：
Guowei Liu;Dan Liu;Zong-jie Li;J. Jiao;Xuewen Hou;Xiaoming Zhang;Qian Che;T. Zhu;Dehai Li-Dehai-L
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文献类型：
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作者：
Guowei Liu;Dan Liu;Zong-jie Li;J. Jiao;Xuewen Hou;Xiaoming Zhang;Qian Che;T. Zhu;Dehai Li-Dehai-L
通过过量表达LaeA类全球转录调控因子和MpaB类生物合成剪裁酶，从海洋真菌互隔交链孢霉JJY-32中发现了四种新的ACTG-毒素，如三环交链孢烯类化合物O-R。其中，三环交替芳烃O具有非正则的环己酮-吡喃稠合呋喃环结构，三环交替芳烃R具有截短的异戊二烯末端。根据一维和二维核磁共振数据并辅以ECD计算，确定了它们的结构。三环交链菌烯O-R在TLR4转染的巨噬细胞(RAW264.7)中显示出较强的抗炎活性。
Four new ACTG-toxins like meroterpenoids tricycloalternarenes O-R were discovered from a marine-derived fungus Alternaria alternata JJY-32 by the overexpression of a LaeA-like global transcriptional regulator and a MpaB-like biosynthetic tailoring enzyme. Among those structures, tricycloalternarene O possesses a non-canonical cyclohexanone-pyran fused furan ring structure and tricycloalternarene R contains a truncated isoprenoid terminal. The structures were elucidated based on comprehensive 1D and 2D NMR data and assisted by ECD calculations. Tricycloalternarenes O-R showed potent anti-inflammatory activity in TLR4-transfected microphage cells (RAW264.7).