Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities
Isolation of new lucilactaene derivatives from P450 monooxygenase and aldehyde dehydrogenase knockout Fusarium sp. RK97-94 strains and their biological activities
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DOI：
10.1038/s41429-022-00529-3
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发表时间：
2022-04-28
影响因子：
3.3
通讯作者：
Osada, Hiroyuki
中科院分区：
文献类型：
--
作者：
Abdelhakim, Islam A.;Motoyama, Takayuki;Osada, Hiroyuki
镰刀菌RK 97 -94是一种有效的抗疟化合物，如Lucilactaene及其衍生物的生产者。已经鉴定了光泽乳烯的生物合成基因簇，但在以前的论文中仅报道了甲基转移酶（luc 1）的敲除突变体。本文报道了从乙醛脱氢酶基因敲除菌株中分离和鉴定前光泽乳烯G（1）和前光泽乳烯H（2（增量luc 3）培养液，以及前光泽乳烯A（3）、前光泽乳烯B（4），以及前光泽乳烯E（5）和前光泽乳烯F（6）的两种异构体混合物，来自P450单加氧酶敲除菌株（增量luc 2）培养液。我们的数据，与以前的不同，表明醛脱氢酶（Luc 3）参与光泽乳烯的生物合成，并支持P450单加氧酶（Luc 2）参与C-20羟基化，而不是C-13-C-14环氧化或C-15羟基化。分离的化合物显示出中等至强的抗疟活性，并研究了Lucilactaene衍生物的构效关系。
Fusarium sp. RK97-94 is a producer of potent antimalarial compounds such as lucilactaene and its derivatives. The biosynthetic gene cluster of lucilactaene was identified but only a knockout mutant of methyltransferase (luc1) was reported in previous papers. Herein, we report on isolation and identification of prelucilactaene G (1), and prelucilactaene H (2) from the aldehyde dehydrogenase knockout strain ( increment luc3) culture broth, as well as prelucilactaene A (3), prelucilactaene B (4), and two isomeric mixtures of prelucilactaene E (5) and prelucilactaene F (6), from the P450 monooxygenase knockout strain ( increment luc2) culture broth. Our data, unlike the previous ones, suggest the involvement of the aldehyde dehydrogenase (Luc3) in lucilactaene biosynthesis, and support the involvement of the P450 monooxygenase (Luc2) in C-20 hydroxylation rather than C-13-C-14 epoxidation or C-15 hydroxylation. Isolated compounds displayed moderate to strong antimalarial activities, and the structure-activity relationship of lucilactaene derivatives was examined.