A Cell Factory of a Fungicolous Fungus Calcarisporium arbuscula for Efficient Production of Natural Products
A Cell Factory of a Fungicolous Fungus Calcarisporium arbuscula for Efficient Production of Natural Products
复制标题
用于高效生产天然产物的真菌 Calcarisporium arbuscula 细胞工厂
DOI：
10.1021/acssynbio.0c00371
复制
发表时间：
2021-03-15
影响因子：
4.7
通讯作者：
Mao, Xu-Ming
中科院分区：
文献类型：
--
作者：
Cheng, Jin-Tao;Yu, Jia-Hui;Mao, Xu-Ming
真菌天然产物是临床药物的丰富来源。特别是真菌类真菌具有大量的生物合成基因簇（BGCs），可以产生大量具有生物活性的天然产物，但大多数BGCs在实验室中是沉默的。我们已经证明了一种真菌Calcarisporium arbuscula NRRL 3705主要产生高度还原的聚酮型真菌毒素aurovertin。在对aurovertin0突变体Delta aurA作为高效宿主进行评估后，我们进一步基于RNA-Seq筛选了两个强启动子aurBp和A07068p，并成功激活了来自C. arbuscula的一个内源基因簇和另外三个来自其他真菌的外源BGCs，以生产聚酮型天然产物。因此，我们展示了一个来自真菌C. arbuscula的高效表达系统，该系统将对传统的曲霉和青霉真菌细胞工厂非常有益和补充，并为从真菌中全基因组挖掘生物活性天然产物提供了有用的工具包。
Fungal natural products are rich sources of clinical drugs. Particularly, the fungicolous fungi have a large number of biosynthetic gene clusters (BGCs) to produce numerous bioactive natural products, but most BGCs are silent in the laboratory. We have shown that a fungicolous fungus Calcarisporium arbuscula NRRL 3705 predominantly produces the highly reduced polyketide-type mycotoxins aurovertins. Here after evaluation of the aurovertin-null mutant Delta aurA as an efficient host, we further screened two strong promoters aurBp and A07068p based on RNA-Seq, and successfully activated an endogenous gene cluster from C. arbuscula as well as three additional exogenous BGCs from other fungi to produce polyketide-type natural products. Thus, we showed an efficient expression system from the fungicolous fungus C. arbuscula, which will be highly beneficial and complementary to the conventional Aspergillus and Penicillium fungal cell factories, and provides a useful toolkit for genome-wide mining of bioactive natural products from fungicolous fungi.