Natural products from filamentous fungi and production by heterologous expression.

Natural products from filamentous fungi and production by heterologous expression.
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来自丝状真菌的天然产物和通过异源表达的生产。

DOI:
10.1007/s00253-016-8034-2
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发表时间:
2017-01
影响因子:
5
通讯作者:
Bailey, Andy M.
Bailey, Andy M.
中科院分区:
工程技术2区
文献类型:
--
作者:
Alberti, Fabrizio;Foster, Gary D.;Bailey, Andy M.

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丝状真菌代表了一个令人难以置信的丰富而又被忽视的天然产物库,这些天然产物通常显示出强大的生物活性并在不同领域中找到应用。在其宿主生产者中增加生物活性代谢物的天然低产量可能是有问题的,并且产量提高进一步受到这些真菌通常是遗传难治性的或具有苛刻的培养条件的阻碍。此外,全合成并不总是代表用于产生生物活性真菌激发的代谢物的具有成本效益的方法,特别是当追求具有复杂化学性质的化合物的组装时。丝状真菌是生物活性化合物合成的有效途径,本文综述了丝状真菌异源生产次生代谢产物的研究进展。许多优点与该技术相关,例如工具的可用性,这些工具允许提高产量并将生物合成导向天然存在的代谢物的类似物。此外,宿主的选择可用于异源表达,从模型单细胞生物到充分表征的丝状真菌,这也已被证明允许研究复杂的次级代谢产物的生物合成。展望未来,真菌很可能继续发挥重要作用,作为新药物和农用化学品的来源,无论是作为新的天然产物的生产者,还是作为通过合成生物学产生新化合物的平台。
Filamentous fungi represent an incredibly rich and rather overlooked reservoir of natural products, which often show potent bioactivity and find applications in different fields. Increasing the naturally low yields of bioactive metabolites within their host producers can be problematic, and yield improvement is further hampered by such fungi often being genetic intractable or having demanding culturing conditions. Additionally, total synthesis does not always represent a cost-effective approach for producing bioactive fungal-inspired metabolites, especially when pursuing assembly of compounds with complex chemistry. This review aims at providing insights into heterologous production of secondary metabolites from filamentous fungi, which has been established as a potent system for the biosynthesis of bioactive compounds. Numerous advantages are associated with this technique, such as the availability of tools that allow enhanced production yields and directing biosynthesis towards analogues of the naturally occurring metabolite. Furthermore, a choice of hosts is available for heterologous expression, going from model unicellular organisms to well-characterised filamentous fungi, which has also been shown to allow the study of biosynthesis of complex secondary metabolites. Looking to the future, fungi are likely to continue to play a substantial role as sources of new pharmaceuticals and agrochemicals—either as producers of novel natural products or indeed as platforms to generate new compounds through synthetic biology.
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期刊: Angewandte Chemie (International ed. in English)
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