Total Heterologous Biosynthesis of Fungal Natural Products in Aspergillus nidulans.
Total Heterologous Biosynthesis of Fungal Natural Products in Aspergillus nidulans.
复制标题
构巢曲霉中真菌天然产物的全杂环生物合成。
DOI：
10.1021/acs.jnatprod.2c00487
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发表时间：
2022-10-28
影响因子：
5.1
通讯作者：
Lin, Tzu-Shyang
中科院分区：
文献类型：
--
作者：
Chiang, Yi-Ming;Wang, Clay C. C.;Lin, Tzu-Shyang
真菌天然产物含有广泛的生物活性化合物，包括重要的药物和农用化学品。有趣的是，对真菌基因组的生物信息学分析表明，真菌有可能产生比迄今发现的更多的天然产品。因此，人们普遍认为，在实验室培养条件下，真菌天然产物的大多数生物合成途径都是沉默的或表达水平很低的。为了利用这一巨大的化学储存库，近年来，在遗传易受控制的真菌宿主中重建完整的生物合成途径(完全异源生物合成)已得到越来越多的应用。本文综述了2020年前利用根癌曲霉作为异源宿主实现真菌天然产物的完全异源生物合成。本文综述了曲霉菌的转化、根瘤曲霉的宿主、穿梭载体和染色体整合表达等方面的研究进展。总而言之，这些工具不仅有助于发现神秘的天然产物，而且还可以用来产生具有清洁代谢物背景的高产菌株。与全合成相比，全异源生物合成提供了一种构建复杂分子的简化策略，并具有商业应用的潜力。
Fungal natural products comprise a wide range of bioactive compounds including important drugs and agrochemicals. Intriguingly, bioinformatic analyses of fungal genomes have revealed that fungi have the potential to produce significantly more natural products than what have been discovered so far. It has thus become widely accepted that most biosynthesis pathways of fungal natural products are silent or expressed at very low levels under laboratory cultivation conditions. To tap into this vast chemical reservoir, the reconstitution of entire biosynthetic pathways in genetically tractable fungal hosts (total heterologous biosynthesis) has become increasingly employed in recent years. This review summarizes total heterologous biosynthesis of fungal natural products accomplished before 2020 using Aspergillus nidulans as heterologous hosts. We review here Aspergillus transformation, A. nidulans hosts, shuttle vectors for episomal expression, and chromosomal integration expression. These tools, collectively, not only facilitate the discovery of cryptic natural products but can also be used to generate high-yield strains with clean metabolite backgrounds. In comparison with total synthesis, total heterologous biosynthesis offers a simplified strategy to construct complex molecules and holds potential for commercial application.
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