{"title":"Discovery and Characterization of a <i>cis</i>-Casbene Diterpene Synthase from <i>Streptomyces paromomycinus</i>.","authors":"Xinru Sun, Fang-Ru Li, Qian Yang, Xingming Pan, Hui-Min Xu, Liao-Bin Dong","doi":"10.1021/acs.jnatprod.5c00870","DOIUrl":null,"url":null,"abstract":"<p><p>Casbene-type diterpenoids are important bioactive natural products, but all known examples possess exclusively <i>trans</i>-configured double bonds. Here, we report the discovery of <i>Sp</i>TS1 from <i>Streptomyces paromomycinus</i>, a diterpene synthase that produces the first naturally occurring <i>cis</i>-casbene. Through heterologous expression and <i>in vitro</i> characterization, we isolated four novel <i>cis</i>-diterpenes from the substrate nerylneryl diphosphate (NNPP): (1<i>S</i>,2<i>Z</i>,6<i>Z</i>,10<i>Z</i>,14<i>S</i>)-casbene (<b>1</b>) featuring the characteristic bicyclo[12.1.0]pentadecane scaffold, 14-membered macrocyclic diterpene <b>2</b>, and two monocyclic diterpenes <b>3</b> and <b>4</b>. The absolute configurations of <b>1</b> and <b>2</b> were established through ECD spectroscopy and quantum calculations. Notably, <i>Sp</i>TS1 also accepts <i>trans</i>-substrate geranylgeranyl diphosphate (GGPP) to produce cembrene-type diterpenes, demonstrating unusual substrate promiscuity. This discovery not only fills an important gap in casbene natural product diversity but also reveals new possibilities for engineering stereochemically diverse terpenoids.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.5c00870","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Casbene-type diterpenoids are important bioactive natural products, but all known examples possess exclusively trans-configured double bonds. Here, we report the discovery of SpTS1 from Streptomyces paromomycinus, a diterpene synthase that produces the first naturally occurring cis-casbene. Through heterologous expression and in vitro characterization, we isolated four novel cis-diterpenes from the substrate nerylneryl diphosphate (NNPP): (1S,2Z,6Z,10Z,14S)-casbene (1) featuring the characteristic bicyclo[12.1.0]pentadecane scaffold, 14-membered macrocyclic diterpene 2, and two monocyclic diterpenes 3 and 4. The absolute configurations of 1 and 2 were established through ECD spectroscopy and quantum calculations. Notably, SpTS1 also accepts trans-substrate geranylgeranyl diphosphate (GGPP) to produce cembrene-type diterpenes, demonstrating unusual substrate promiscuity. This discovery not only fills an important gap in casbene natural product diversity but also reveals new possibilities for engineering stereochemically diverse terpenoids.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.