Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids.

Synthetic biology, combinatorial biosynthesis, and chemo‑enzymatic synthesis of isoprenoids.
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DOI:
10.1007/s10295-020-02306-3
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发表时间:
2020-10
影响因子:
3.4
通讯作者:
Williams GJ
Williams GJ
中科院分区:
工程技术3区
文献类型:
--
作者:
Malico AA;Calzini MA;Gayen AK;Williams GJ

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类异戊二烯是一类天然产物,作为生物活性化合物和商业化合物具有无数应用。它们的不同结构来自于生物合成组装和剪裁它们的支架,最终由两个C5半萜构建块构建。这些平台的模块逻辑可以用来提高不同宿主中有价值的类异戊二烯的效价,并产生新的天然化合物。通常,该过程由组分酶的底物或产物混杂促进,可以利用这些酶来生产新型类异戊二烯。为了补充类异戊二烯生物合成的合理增强甚至重新编程,正在开发依赖于搜索大型酶文库的高通量方法。本文综述了近五年来类异戊二烯合成生物学、组合生物合成和化学-酶促合成的研究进展和策略。包括无细胞生物合成和高通量工具的新兴应用,最终在类异戊二烯生物合成工程的未来前景和前景的讨论。
Isoprenoids are a large class of natural products with myriad applications as bioactive and commercial compounds. Their diverse structures are derived from the biosynthetic assembly and tailoring of their scaffolds, ultimately constructed from two C5 hemiterpene building blocks. The modular logic of these platforms can be harnessed to improve titers of valuable isoprenoids in diverse hosts and to produce new-to-nature compounds. Often, this process is facilitated by the substrate or product promiscuity of the component enzymes, which can be leveraged to produce novel isoprenoids. To complement rational enhancements and even re-programming of isoprenoid biosynthesis, high-throughput approaches that rely on searching through large enzymatic libraries are being developed. This review summarizes recent advances and strategies related to isoprenoid synthetic biology, combinatorial biosynthesis, and chemo-enzymatic synthesis, focusing on the last five years. Emerging applications of cell-free biosynthesis and high-throughput tools are included that culminate in a discussion of the future outlook and perspective of isoprenoid biosynthetic engineering.
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