关键词: bacterial sesquiterpenes and diterpenes cytochrome P450 pathway engineering synthetic biology terpene biosynthesis terpene cyclase

来  源:   DOI:10.3762/bjoc.15.283   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our knowledge of how they are biosynthesized is limited, particularly when compared to the well-studied thiotemplate assembly lines. Bacteria have only recently been recognized as having the genetic potential to biosynthesize a large number of complex terpenoids, but our current ability to associate genetic potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This functional promiscuity of terpene biosynthetic pathways renders terpene biosynthesis susceptible to rational pathway engineering using the latest developments in the field of synthetic biology. These engineered pathways will not only facilitate the rational creation of both known and novel terpenoids, their development will deepen our understanding of a significant branch of biosynthesis. The biosynthetic insights gained will likely empower a greater degree of engineering proficiency for non-natural terpene biosynthetic pathways and pave the way towards the biotechnological production of high value terpenoids.
摘要:
萜类化合物是最大的和结构上最多样化的一类天然产物。它们在多种检测和对抗疾病中具有有效和特异的生物活性,包括癌症和疟疾作为著名的例子。虽然被表征的萜类分子的数量是巨大的,我们对它们如何生物合成的知识是有限的,特别是与经过充分研究的thiotemplate装配线相比。细菌最近才被认为具有生物合成大量复杂萜类化合物的遗传潜力,但是我们目前将遗传潜力与分子结构联系起来的能力受到了严重的限制。典型的萜烯生物合成途径使用单一酶形成环化的烃主链,然后用一套定制酶进行修饰,所述定制酶可以从单一主链产生数十种不同的产物。萜烯生物合成途径的这种功能混杂性使得萜烯生物合成易于使用合成生物学领域的最新发展进行合理途径工程。这些工程途径不仅有助于已知和新型萜类化合物的合理创造,它们的发展将加深我们对生物合成的一个重要分支的理解。获得的生物合成见解可能会使非天然萜烯生物合成途径的工程熟练程度更高,并为高价值萜类化合物的生物技术生产铺平道路。
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