Alsup Tyler A, Li Zining, McCadden Caitlin A, Jagels Annika, Łomowska-Keehner Diana P, Marshall Erin M, Dong Liao-Bin, Loesgen Sandra, Rudolf Jeffrey D
Department of Chemistry, University of Florida Gainesville Florida USA
Whitney Laboratory for Marine Bioscience, University of Florida St. Augustine FL USA.
RSC Chem Biol. 2024 Aug 5;5(10):1010-6. doi: 10.1039/d4cb00138a.
The chemical logic associated with assembly of many bacterial terpenoids remains poorly understood. We focused our efforts on the early-stage biosynthesis of the phenalinolactone diterpenoids, demonstrating that the -perhydrophenanthrene core is constructed by sequential prenylation, epoxidation, and cyclization. The functions and timing of PlaT1-PlaT3 were assigned by comprehensive heterologous reconstitution. We illustrated that the UbiA prenyltransferase PlaT3 acts on geranylgeranyl diphosphate (GGPP) in the first step of phenalinolactone biosynthesis, prior to epoxidation by the flavin-dependent monooxygenase PlaT1 and cyclization by the type II terpene cyclase PlaT2. Finally, we isolated eight new-to-nature terpenoids, expanding the scope of the bacterial terpenome. The biosynthetic strategy employed in the assembly of the phenalinolactone core, with cyclization occurring after prenylation, is rare in bacteria and resembles fungal meroterpenoid biosynthesis. The findings presented here set the stage for future discovery, engineering, and enzymology efforts in bacterial meroterpenoids.
与许多细菌萜类化合物组装相关的化学逻辑仍知之甚少。我们将研究重点放在了苯那内酯二萜类化合物的早期生物合成上，证明了全氢菲核心是通过依次进行异戊烯基化、环氧化和环化构建而成的。通过全面的异源重组确定了PlaT1 - PlaT3的功能和作用时机。我们阐明了泛醌A异戊烯基转移酶PlaT3在苯那内酯生物合成的第一步作用于香叶基香叶基二磷酸（GGPP），这发生在黄素依赖性单加氧酶PlaT1进行环氧化和II型萜烯环化酶PlaT2进行环化之前。最后，我们分离出了8种新的天然萜类化合物，扩大了细菌萜类化合物组的范围。苯那内酯核心组装过程中采用的生物合成策略，即异戊烯基化后进行环化，在细菌中很少见，类似于真菌杂萜类生物合成。本文的研究结果为细菌杂萜类化合物未来的发现、工程改造和酶学研究奠定了基础。
