Yin Ying, Fu Qiang, Wu Wenhui, Cai Menghao, Zhou Xiangshan, Zhang Yuanxing
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 300 Feng Lin Road, Shanghai 200032, China.
Mar Drugs. 2017 Jul 5;15(7):214. doi: 10.3390/md15070214.
Many fungi in the genus can produce various isoindolinone derivatives. These compounds are formed by a spontaneous reaction between a phthalic aldehyde precursor and an ammonium ion or amino compounds. In this study, we suggested the isoindolinone biosynthetic gene cluster in by genome mining based on three reported core genes. Remarkably, there is an additional nitrate reductase (NR) gene copy in the proposed cluster. NR is the rate-limiting enzyme of nitrate reduction. Accordingly, this cluster was speculated to play a role in the balance of ammonium ion concentration in . Ammonium ions can be replaced by different amino compounds to create structural diversity in the biosynthetic process of isoindolinone. We tested a rational supply of amino compounds ((±)-3-amino-2-piperidinone, glycine, and l-threonine) in the culture of an isoindolinone high-producing marine fungus, FG216. As a result, we obtained four new kinds of isoindolinone derivatives (FGFC4-GFC7) by this method. Furthermore, high yields of FGFC4-FGFC7 confirmed the outstanding production capacity of FG216. Among the four new isoindolinone derivatives, FGFC6 and FGFC7 showed promising fibrinolytic activities. The knowledge of biosynthesis pathways may be an important attribute for the discovery of novel bioactive marine natural products.
该属中的许多真菌能够产生各种异吲哚啉酮衍生物。这些化合物是由邻苯二甲醛前体与铵离子或氨基化合物之间的自发反应形成的。在本研究中，我们基于三个已报道的核心基因，通过基因组挖掘推测了[具体真菌名称未给出]中的异吲哚啉酮生物合成基因簇。值得注意的是，在所提出的基因簇中存在一个额外的硝酸还原酶（NR）基因拷贝。NR是硝酸盐还原的限速酶。因此，推测该基因簇在[具体真菌名称未给出]中铵离子浓度的平衡中发挥作用。在异吲哚啉酮的生物合成过程中，铵离子可以被不同的氨基化合物取代以产生结构多样性。我们在异吲哚啉酮高产海洋真菌[具体真菌名称未给出] FG216的培养中测试了氨基化合物（（±）-3-氨基-2-哌啶酮、甘氨酸和L-苏氨酸）的合理供应。结果，通过这种方法我们获得了四种新的异吲哚啉酮衍生物（FGFC4 - GFC7）。此外，FGFC4 - FGFC7的高产率证实了FG216出色的生产能力。在这四种新的异吲哚啉酮衍生物中，FGFC6和FGFC7表现出有前景的纤溶活性。生物合成途径的知识可能是发现新型生物活性海洋天然产物的一个重要因素。
