Max-Planck Institute for Chemical Ecology, Department of Natural Product Biosynthesis, Hans-Knoll Strasse 8, 07745, Jena, Germany.
Center for Applied Genetic Technologies, University of Georgia, Athens, GA, USA.
Nat Commun. 2022 Aug 11;13(1):4718. doi: 10.1038/s41467-022-32414-w.
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.
数千种天然产物源自融合的环戊烷-吡喃分子支架法呢醇内酯。这些天然产物在农业和医疗行业等广泛领域得到应用。例如，法呢醇内酯的氧化衍生物法呢内酯酮，以其作为猫诱引剂的特性以及作为驱虫剂的潜力而闻名。这些天然存在的法呢醇内酯衍生化合物大多仅来自于八种可能的立体异构体中的两种，即 7S-顺式-反式和 7R-顺式-顺式法呢醇内酯。在这里，我们使用天然存在和工程化酶的组合来生产八种可能的法呢醇内酯或法呢内酯酮立体异构体中的七种。这些酶为生物催化生产更广泛的环烯醚萜类化合物开辟了可能性，为这一重要天然产物支架的多样化提供了一个多功能系统。
