• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

通过立体化学控制的组合生物合成拓展二萜结构多样性的范畴

Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.

作者信息

Andersen-Ranberg Johan, Kongstad Kenneth Thermann, Nielsen Morten Thrane, Jensen Niels Bjerg, Pateraki Irini, Bach Søren Spanner, Hamberger Britta, Zerbe Philipp, Staerk Dan, Bohlmann Jörg, Møller Birger Lindberg, Hamberger Björn

机构信息

Department of Plant and Environmental Sciences, Center for Synthetic Biology, Thorvaldsensvej 40, 1871, København, Denmark.

Natural Products Research, University of Copenhagen, Denmark.

出版信息

Angew Chem Int Ed Engl. 2016 Feb 5;55(6):2142-6. doi: 10.1002/anie.201510650. Epub 2016 Jan 8.

DOI:10.1002/anie.201510650
PMID:26749264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4755150/
Abstract

Plant-derived diterpenoids serve as important pharmaceuticals, food additives, and fragrances, yet their low natural abundance and high structural complexity limits their broader industrial utilization. By mimicking the modularity of diterpene biosynthesis in plants, we constructed 51 functional combinations of class I and II diterpene synthases, 41 of which are "new-to-nature". Stereoselective biosynthesis of over 50 diterpene skeletons was demonstrated, including natural variants and novel enantiomeric or diastereomeric counterparts. Scalable biotechnological production for four industrially relevant targets was accomplished in engineered strains of Saccharomyces cerevisiae.

摘要

植物源二萜类化合物是重要的药物、食品添加剂和香料，但其天然丰度低且结构复杂，限制了它们在更广泛工业领域的应用。通过模拟植物中二萜生物合成的模块化，我们构建了51种I类和II类二萜合酶的功能组合，其中41种是“自然界新发现的”。我们证明了50多种二萜骨架的立体选择性生物合成，包括天然变体以及新的对映体或非对映体对应物。在酿酒酵母工程菌株中实现了四种与工业相关目标产物的可扩展生物技术生产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/d858fa1e36c6/ANIE-55-2142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/8f947567b3b2/ANIE-55-2142-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/21a42ced6ac5/ANIE-55-2142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/d858fa1e36c6/ANIE-55-2142-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/8f947567b3b2/ANIE-55-2142-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/21a42ced6ac5/ANIE-55-2142-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e80/4755150/d858fa1e36c6/ANIE-55-2142-g002.jpg

相似文献

1
Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.通过立体化学控制的组合生物合成拓展二萜结构多样性的范畴
Angew Chem Int Ed Engl. 2016 Feb 5;55(6):2142-6. doi: 10.1002/anie.201510650. Epub 2016 Jan 8.
2
Combinatorial biosynthesis in yeast leads to over 200 diterpenoids.酵母中的组合生物合成导致了超过 200 种二萜类化合物的产生。
Metab Eng. 2024 Mar;82:193-200. doi: 10.1016/j.ymben.2024.02.006. Epub 2024 Feb 20.
3
Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast.在酵母中重建月桂烷型二萜生物合成的化学多样性。
Metab Eng. 2015 Mar;28:91-103. doi: 10.1016/j.ymben.2014.12.001. Epub 2014 Dec 10.
4
Cytochrome P450 enzymes: A driving force of plant diterpene diversity.细胞色素 P450 酶：植物二萜多样性的驱动力。
Phytochemistry. 2019 May;161:149-162. doi: 10.1016/j.phytochem.2018.12.003. Epub 2019 Feb 5.
5
Plant diterpene synthases: exploring modularity and metabolic diversity for bioengineering.植物二萜合酶：探索模块化和代谢多样性用于生物工程。
Trends Biotechnol. 2015 Jul;33(7):419-28. doi: 10.1016/j.tibtech.2015.04.006. Epub 2015 May 20.
6
Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture.发现并功能表征薰衣草（Salvia sclarea (L.)）中用于合成鼠尾草烯醇的两种二萜合酶及其与香水制造的相关性。
BMC Plant Biol. 2012 Jul 26;12:119. doi: 10.1186/1471-2229-12-119.
7
Engineering chimeric diterpene synthases and isoprenoid biosynthetic pathways enables high-level production of miltiradiene in yeast.工程嵌合二萜合酶和异戊烯基生物合成途径使酵母中高水平产生米特里迪烯。
Metab Eng. 2020 Jul;60:87-96. doi: 10.1016/j.ymben.2020.03.011. Epub 2020 Apr 5.
8
Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase.通过将 Erg20p 工程化为香叶基香叶基二磷酸合酶，在酵母中高效生产二萜。
Metab Eng. 2015 Jan;27:65-75. doi: 10.1016/j.ymben.2014.10.008. Epub 2014 Nov 7.
9
Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis.一种细菌和一种植物二萜合酶的极端混杂性实现了组合生物合成。
Metab Eng. 2016 Sep;37:24-34. doi: 10.1016/j.ymben.2016.04.001. Epub 2016 Apr 7.
10
Functional characterization of the cytochrome P450 monooxygenase CYP71AU87 indicates a role in marrubiin biosynthesis in the medicinal plant Marrubium vulgare.细胞色素 P450 单加氧酶 CYP71AU87 的功能表征表明其在药用植物毛毡草中马里苷生物合成中的作用。
BMC Plant Biol. 2019 Mar 25;19(1):114. doi: 10.1186/s12870-019-1702-5.

引用本文的文献

1
Progress and prospects in metabolic engineering approaches for isoprenoid biosynthesis in microalgae.微藻中类异戊二烯生物合成的代谢工程方法进展与展望
Biotechnol Biofuels Bioprod. 2025 Jun 18;18(1):64. doi: 10.1186/s13068-025-02665-y.
2
A high-quality genome assembly of the tetraploid Teucrium chamaedrys unveils a recent whole-genome duplication and a large biosynthetic gene cluster for diterpenoid metabolism.四倍体石蚕的高质量基因组组装揭示了近期的全基因组复制以及一个用于二萜类代谢的大型生物合成基因簇。
Plant Commun. 2025 Aug 11;6(8):101393. doi: 10.1016/j.xplc.2025.101393. Epub 2025 Jun 3.
3
Entry Steps in the Biosynthetic Pathway to Diterpenoid Alkaloids in and .

本文引用的文献

1
Plant diterpene synthases: exploring modularity and metabolic diversity for bioengineering.植物二萜合酶：探索模块化和代谢多样性用于生物工程。
Trends Biotechnol. 2015 Jul;33(7):419-28. doi: 10.1016/j.tibtech.2015.04.006. Epub 2015 May 20.
2
Identification of a new diterpene biosynthetic gene cluster that produces O-methylkolavelool in Herpetosiphon aurantiacus.在橙色滑柱菌中鉴定出一个产生O-甲基科拉韦醇的新二萜生物合成基因簇。
Chembiochem. 2015 Mar 23;16(5):772-81. doi: 10.1002/cbic.201402652. Epub 2015 Feb 18.
3
Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast.
中乌头属和乌头属中二萜生物碱生物合成途径的起始步骤
bioRxiv. 2025 May 17:2025.05.15.654307. doi: 10.1101/2025.05.15.654307.
4
Expansion of the Stereochemical Space of Triterpenes by Mining Noncanonical Oxidosqualene Cyclases Across the Diversity of Green Plants.通过挖掘绿色植物多样性中的非经典氧化角鲨烯环化酶扩展三萜类化合物的立体化学空间
J Am Chem Soc. 2025 Mar 26;147(12):10320-10330. doi: 10.1021/jacs.4c16956. Epub 2025 Mar 13.
5
Plants against cancer: towards green Taxol production through pathway discovery and metabolic engineering.植物对抗癌症：通过途径发现和代谢工程实现绿色紫杉醇生产。
aBIOTECH. 2024 May 26;5(3):394-402. doi: 10.1007/s42994-024-00170-8. eCollection 2024 Sep.
6
CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family.CYP76BK1 同源物在薄荷科的环烯醚萜类化合物中催化呋喃和内酯环的形成。
Plant J. 2024 Nov;120(3):984-997. doi: 10.1111/tpj.17031. Epub 2024 Sep 14.
7
CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family.细胞色素P450 76BK1直系同源物催化整个薄荷科克罗烷二萜中呋喃环和内酯环的形成。
bioRxiv. 2024 Aug 29:2024.08.28.609960. doi: 10.1101/2024.08.28.609960.
8
Characterization of switchgrass (Panicum virgatum L.) PvKSL1 as a levopimaradiene/abietadiene-type diterpene synthase.柳枝稷（Panicum virgatum L.）PvKSL1作为左旋海松二烯/枞二烯型二萜合酶的特性分析
Plant Biol (Stuttg). 2024 Aug 20. doi: 10.1111/plb.13708.
9
Engineering for the production of diterpenoid compounds.用于二萜类化合物生产的工程技术。
mLife. 2023 Dec 26;2(4):428-437. doi: 10.1002/mlf2.12097. eCollection 2023 Dec.
10
Compartmentalized Terpenoid Production in Plants Using Agrobacterium-Mediated Transient Expression.利用农杆菌介导的瞬时表达在植物中进行隔室化萜类生产。
Methods Mol Biol. 2024;2760:21-34. doi: 10.1007/978-1-0716-3658-9_2.
在酵母中重建月桂烷型二萜生物合成的化学多样性。
Metab Eng. 2015 Mar;28:91-103. doi: 10.1016/j.ymben.2014.12.001. Epub 2014 Dec 10.
4
Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare.唇形科植物筋骨草中具有生物活性的二萜类化合物生物合成体系的二萜合酶。
Plant J. 2014 Sep;79(6):914-27. doi: 10.1111/tpj.12589. Epub 2014 Jul 23.
5
Omnia praeclara rara. The quest for ingenol heats up.一切卓越之物皆稀少。对大戟醇的探索热度升温。
Angew Chem Int Ed Engl. 2014 Jan 20;53(4):927-9. doi: 10.1002/anie.201308281.
6
Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes.迷迭香叶腺毛中松香烷型二萜生物合成的两个基因的表征。
Phytochemistry. 2014 May;101:52-64. doi: 10.1016/j.phytochem.2014.01.021. Epub 2014 Feb 22.
7
Manoyl oxide (13R), the biosynthetic precursor of forskolin, is synthesized in specialized root cork cells in Coleus forskohlii.毛喉素氧化物（13R），即福斯高林的生物合成前体，在毛喉鞘蕊花的特化根皮细胞中合成。
Plant Physiol. 2014 Mar;164(3):1222-36. doi: 10.1104/pp.113.228429. Epub 2014 Jan 30.
8
14-step synthesis of (+)-ingenol from (+)-3-carene.（+）-3-蒈烯经 14 步反应合成（+）- Ingenol。
Science. 2013 Aug 23;341(6148):878-82. doi: 10.1126/science.1241606. Epub 2013 Aug 1.
9
Gene discovery of modular diterpene metabolism in nonmodel systems.非模式系统中模块化二萜代谢的基因发现。
Plant Physiol. 2013 Jun;162(2):1073-91. doi: 10.1104/pp.113.218347. Epub 2013 Apr 23.
10
High-level semi-synthetic production of the potent antimalarial artemisinin.高效半合成制备强效抗疟药物青蒿素。
Nature. 2013 Apr 25;496(7446):528-32. doi: 10.1038/nature12051. Epub 2013 Apr 10.