Biocatalytic routes to stereo-divergent iridoids.

Biocatalytic routes to stereo-divergent iridoids.
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DOI:
10.1038/s41467-022-32414-w
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发表时间:
2022-08-11
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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成千上万的天然产物是从稠合环戊烷-吡喃分子支架荆芥内酯醇衍生而来的。这些天然产品被广泛应用于农业和医疗行业。例如,荆芥内酯,荆芥内酯醇的氧化衍生物,因其猫引诱剂特性以及作为驱虫剂的潜力而闻名。这些天然存在的荆芥内酯衍生化合物中的大多数仅来自八种可能的立体异构体中的两种,7S-顺式-反式和7 R-顺式-顺式荆芥内酯醇。在这里,我们使用天然存在的和工程酶的组合,以产生七个可能的荆芥内酯或荆芥内酯立体异构体的八个。这些酶打开了生物催化生产更广泛的环烯醚萜类化合物的可能性,为这一重要的天然产物支架的多样化提供了一个通用的系统。环烯醚萜类化合物是一类重要的天然产物。在这里,作者报告了荆芥内酯相关的短链还原酶的发现和工程及其在荆芥内酯或荆芥内酯立体异构体生物合成中的应用,作为生产环烯醚萜天然产物支架的通用系统。
Thousands of natural products are derived from the fused cyclopentane-pyran molecular scaffold nepetalactol. These natural products are used in an enormous range of applications that span the agricultural and medical industries. For example, nepetalactone, the oxidized derivative of nepetalactol, is known for its cat attractant properties as well as potential as an insect repellent. Most of these naturally occurring nepetalactol-derived compounds arise from only two out of the eight possible stereoisomers, 7S-cis-trans and 7R-cis-cis nepetalactols. Here we use a combination of naturally occurring and engineered enzymes to produce seven of the eight possible nepetalactol or nepetalactone stereoisomers. These enzymes open the possibilities for biocatalytic production of a broader range of iridoids, providing a versatile system for the diversification of this important natural product scaffold. Iridoid compounds are an important class of natural products. Here, the authors report on the discovery and engineering of nepetalactol-related short chain reductases and their application for the biosynthesis of nepetalactol or nepetalactone stereoisomers, as a versatile system for the production of the iridoid natural product scaffold.
用于从头生产环烯醚萜类化合物的米曲霉生物合成平台
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