School of Marine Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Org Lett. 2024 Aug 9;26(31):6692-6697. doi: 10.1021/acs.orglett.4c02372. Epub 2024 Jul 26.
Asperalins represent a novel class of viridicatin natural products with potent inhibitory activities against fish pathogens. In this study, we elucidated the biosynthesis of asperalins in the NSAR1 heterologous host and identified the FAD-dependent monooxygenase AplB stereoselectively hydroxylates viridicatin to yield a unique 3,4 configuration. The monomodular NRPS AplJ catalyzes a rare intramolecular ester bond formation reaction using dihydroquinoline as a nucleophile. Subsequent modifications by cytochrome P450 AplF, chlorinase AplN, and prenyltransferase AplE tailor the anthranilic acid portion, leading to the formation of asperalins. Additionally, we explored the potential of AplB for the hydroxylation of viridicatin analogs, demonstrating its relaxed substrate specificity. This finding suggests that AplB could be developed as a biocatalyst for the synthesis of viridicatin derivatives.
asperalins 代表了一类新型的 viridicatin 天然产物，对鱼类病原体具有很强的抑制活性。在这项研究中，我们阐明了 asperalins 在 NSAR1 异源宿主中的生物合成，并鉴定了 FAD 依赖性单加氧酶 AplB 对 viridicatin 进行立体选择性羟基化，生成独特的 3,4 构型。单模块 NRPS AplJ 使用二氢喹啉作为亲核试剂催化罕见的分子内酯键形成反应。随后，细胞色素 P450 AplF、氯仿酶 AplN 和 prenyltransferase AplE 通过对 anthranilic acid 部分进行修饰，形成 asperalins。此外，我们还探索了 AplB 对 viridicatin 类似物进行羟基化的潜力，证明了其对底物的特异性较为宽松。这一发现表明，AplB 可以作为合成 viridicatin 衍生物的生物催化剂进行开发。
