Nicholson Matthew J, Eaton Carla J, Stärkel Cornelia, Tapper Brian A, Cox Murray P, Scott Barry
Institute of Fundamental Sciences, Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand.
AgResearch, Grasslands Research Centre, Private Bag 11 008, Palmerston North 4442, New Zealand.
Toxins (Basel). 2015 Jul 23;7(8):2701-22. doi: 10.3390/toxins7082701.
The penitremane and janthitremane families of indole-diterpenes are abundant natural products synthesized by Penicillium crustosum and P. janthinellum. Using a combination of PCR, cosmid library screening, and Illumina sequencing we have identified gene clusters encoding enzymes for the synthesis of these compounds. Targeted deletion of penP in P. crustosum abolished the synthesis of penitrems A, B, D, E, and F, and led to accumulation of paspaline, a key intermediate for paxilline biosynthesis in P. paxilli. Similarly, deletion of janP and janD in P. janthinellum abolished the synthesis of prenyl-elaborated indole-diterpenes, and led to accumulation in the latter of 13-desoxypaxilline, a key intermediate for the synthesis of the structurally related aflatremanes synthesized by Aspergillus flavus. This study helps resolve the genetic basis for the complexity of indole-diterpene natural products found within the Penicillium and Aspergillus species. All indole-diterpene gene clusters identified to date have a core set of genes for the synthesis of paspaline and a suite of genes encoding multi-functional cytochrome P450 monooxygenases, FAD dependent monooxygenases, and prenyl transferases that catalyse various regio- and stereo- specific oxidations that give rise to the diversity of indole-diterpene products synthesized by this group of fungi.
吲哚二萜类的青霉震颤素和紫青震颤素家族是由 crustosum 青霉和紫青霉合成的丰富天然产物。通过聚合酶链式反应（PCR）、黏粒文库筛选和 Illumina 测序相结合的方法，我们鉴定出了编码这些化合物合成酶的基因簇。在 crustosum 青霉中靶向缺失 penP 基因，消除了青霉震颤素 A、B、D、E 和 F 的合成，并导致雀稗碱的积累，雀稗碱是紫青霉中鬼笔环肽生物合成的关键中间体。同样，在紫青霉中缺失 janP 和 janD 基因，消除了异戊烯基修饰的吲哚二萜类化合物的合成，并导致后者积累 13-脱氧鬼笔环肽，13-脱氧鬼笔环肽是黄曲霉合成结构相关的黄曲霉素的关键中间体。这项研究有助于解决在青霉和曲霉属物种中发现的吲哚二萜类天然产物复杂性的遗传基础问题。迄今为止鉴定出的所有吲哚二萜类基因簇都有一组核心基因用于合成雀稗碱，以及一组编码多功能细胞色素 P450 单加氧酶、FAD 依赖性单加氧酶和异戊烯基转移酶的基因，这些酶催化各种区域和立体特异性氧化反应，从而产生由这组真菌合成的吲哚二萜类产物的多样性。
