合成生物学方法在天然产物生物合成中的应用。
Synthetic biological approaches to natural product biosynthesis.
机构信息
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA 90095, United States.
出版信息
Curr Opin Biotechnol. 2012 Oct;23(5):736-43. doi: 10.1016/j.copbio.2011.12.016. Epub 2012 Jan 3.
Abstract
Small molecules produced in Nature possess exquisite chemical diversity and continue to be an inspiration for the development of new therapeutic agents. In their host organisms, natural products are assembled and modified using dedicated biosynthetic pathways. By rationally reprogramming and manipulating these pathways, unnatural metabolites containing enhanced structural features that were otherwise inaccessible can be obtained. Additionally, new chemical entities can be synthesized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds.
摘要
自然界中产生的小分子具有精致的化学多样性，并且继续为开发新的治疗药物提供灵感。在其宿主生物中，天然产物使用专用的生物合成途径进行组装和修饰。通过合理地重新编程和操纵这些途径，可以获得具有增强的结构特征的非天然代谢物，这些特征在其他情况下是无法获得的。此外，通过将执行这些复杂化学反应的酶开发成生物催化剂，也可以合成新的化学实体。在这篇综述中，我们将讨论各种组合生物合成策略、它们的技术挑战，并重点介绍一些最近（自 2007 年以来）合理设计的代谢物的例子，以及为生产和修饰临床重要药物化合物而建立的平台。
相似文献
1
Synthetic biological approaches to natural product biosynthesis.合成生物学方法在天然产物生物合成中的应用。
Curr Opin Biotechnol. 2012 Oct;23(5):736-43. doi: 10.1016/j.copbio.2011.12.016. Epub 2012 Jan 3.
2
Reinvigorating natural product combinatorial biosynthesis with synthetic biology.用合成生物学重振天然产物组合生物合成。
Nat Chem Biol. 2015 Sep;11(9):649-59. doi: 10.1038/nchembio.1893.
3
New chemistry from natural product biosynthesis.天然产物生物合成中的新化学。
Biochem Soc Trans. 2016 Jun 15;44(3):738-44. doi: 10.1042/BST20160063.
4
Recent advances in combinatorial biosynthesis for drug discovery.药物发现中组合生物合成的最新进展。
Drug Des Devel Ther. 2015 Feb 12;9:823-33. doi: 10.2147/DDDT.S63023. eCollection 2015.
5
Synthetic biology strategies for microbial biosynthesis of plant natural products.合成生物学策略在植物天然产物的微生物生物合成中的应用。
Nat Commun. 2019 May 13;10(1):2142. doi: 10.1038/s41467-019-09848-w.
6
Synthetic Biology Approaches to New Bisindoles.新型双吲哚的合成生物学方法
Methods Enzymol. 2016;575:21-37. doi: 10.1016/bs.mie.2016.02.017. Epub 2016 Mar 24.
7
Three Principles of Diversity-Generating Biosynthesis.多样性生成生物合成的三个原则。
Acc Chem Res. 2017 Oct 17;50(10):2569-2576. doi: 10.1021/acs.accounts.7b00330. Epub 2017 Sep 11.
8
DNA assembly techniques for next-generation combinatorial biosynthesis of natural products.用于下一代组合生物合成天然产物的 DNA 组装技术。
J Ind Microbiol Biotechnol. 2014 Feb;41(2):469-77. doi: 10.1007/s10295-013-1358-3. Epub 2013 Oct 15.
9
Synthetic biology for natural product drug production and engineering.合成生物学在天然产物药物生产和工程中的应用。
Curr Opin Chem Biol. 2020 Oct;58:137-145. doi: 10.1016/j.cbpa.2020.09.006. Epub 2020 Oct 29.
10
Opportunities for enzyme engineering in natural product biosynthesis.天然产物生物合成中的酶工程机遇。
Curr Opin Chem Biol. 2009 Feb;13(1):35-42. doi: 10.1016/j.cbpa.2009.01.005. Epub 2009 Feb 5.
引用本文的文献
1
Production of the Sesquiterpene Bisabolene From One- and Two-Carbon Compounds in Engineered Methanosarcina acetivorans.在工程化嗜乙酸甲烷八叠球菌中由一碳和二碳化合物生产倍半萜红没药烯
Microb Biotechnol. 2025 Feb;18(2):e70105. doi: 10.1111/1751-7915.70105.
2
Engineering a promiscuous prenyltransferase for selective biosynthesis of an undescribed bioactive cannabinoid analog.构建一种多底物异戊烯基转移酶用于选择性生物合成一种未描述的生物活性大麻素类似物。
Commun Biol. 2025 Feb 4;8(1):173. doi: 10.1038/s42003-025-07509-x.
3
Microbe-assisted fabrication of circularly polarized luminescent bacterial cellulosic hybrids.微生物辅助制备圆偏振发光细菌纤维素杂化物。
Nat Commun. 2025 Jan 29;16(1):1115. doi: 10.1038/s41467-025-56253-7.
4
Engineering Siderophore Biosynthesis and Regulation Pathways to Increase Diversity and Availability.工程化铁载体生物合成和调控途径以增加多样性和可用性。
Biomolecules. 2023 Jun 7;13(6):959. doi: 10.3390/biom13060959.
5
A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast.建立酵母中天然产物可持续制造综合平台的路线图。
Nat Commun. 2023 Apr 6;14(1):1916. doi: 10.1038/s41467-023-37627-1.
6
Recent Advancements in Microbial Polysaccharides: Synthesis and Applications.微生物多糖的最新进展：合成与应用
Polymers (Basel). 2021 Nov 26;13(23):4136. doi: 10.3390/polym13234136.
7
Putative role of natural products as Protein Kinase C modulator in different disease conditions.天然产物作为蛋白激酶 C 调节剂在不同疾病状况中的推测作用。
Daru. 2021 Dec;29(2):397-414. doi: 10.1007/s40199-021-00401-z. Epub 2021 Jul 3.
8
A study on the structure, mechanism, and biochemistry of kanamycin B dioxygenase (KanJ)-an enzyme with a broad range of substrates.卡那霉素 B 双加氧酶（KanJ）的结构、机制和生物化学研究——一种具有广泛底物范围的酶。
FEBS J. 2021 Feb;288(4):1366-1386. doi: 10.1111/febs.15462. Epub 2020 Jul 27.
9
Plant tissue culture as a perpetual source for production of industrially important bioactive compounds.植物组织培养作为生产具有工业重要性的生物活性化合物的永久来源。
Biotechnol Rep (Amst). 2020 Apr 20;26:e00450. doi: 10.1016/j.btre.2020.e00450. eCollection 2020 Jun.
10
Clinical efficacy of implementing Bio Immune(G)ene MEDicine in the treatment of chronic asthma with the objective of reducing or removing effectively corticosteroid therapy: A novel approach and promising results.实施生物免疫（G）基因药物治疗慢性哮喘以有效减少或停用皮质类固醇疗法的临床疗效：一种新方法及令人鼓舞的结果。
Exp Ther Med. 2018 Jun;15(6):5133-5140. doi: 10.3892/etm.2018.6019. Epub 2018 Apr 2.
本文引用的文献
1
Mutant malonyl-CoA synthetases with altered specificity for polyketide synthase extender unit generation.具有改变的聚酮合酶延伸单位生成特异性的突变丙二酰辅酶 A 合成酶。
Chembiochem. 2011 Oct 17;12(15):2289-93. doi: 10.1002/cbic.201100383.
2
Metabolic engineering for the production of natural products.代谢工程在天然产物生产中的应用。
Annu Rev Chem Biomol Eng. 2011;2:211-36. doi: 10.1146/annurev-chembioeng-061010-114209.
3
Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity.超越丙二酰辅酶 A：丙二酰辅酶 A 羧化酶/还原酶同源物在扩大聚酮化合物多样性方面的功能作用。
Nat Prod Rep. 2012 Jan;29(1):72-86. doi: 10.1039/c1np00082a. Epub 2011 Nov 29.
4
Ribosomal route to small-molecule diversity.核糖体通向小分子多样性的途径。
J Am Chem Soc. 2012 Jan 11;134(1):418-25. doi: 10.1021/ja208278k. Epub 2011 Dec 22.
5
Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor.重编程色氨酸卤化酶以优先氯化直接生物碱前体。
J Am Chem Soc. 2011 Dec 7;133(48):19346-9. doi: 10.1021/ja2089348. Epub 2011 Nov 11.
6
Protein engineering towards natural product synthesis and diversification.蛋白质工程在天然产物合成与多样化中的应用。
J Ind Microbiol Biotechnol. 2012 Feb;39(2):227-41. doi: 10.1007/s10295-011-1044-2. Epub 2011 Oct 18.
7
Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation.发现卡那霉素生物合成的平行途径可实现抗生素的人工干预。
Nat Chem Biol. 2011 Oct 9;7(11):843-52. doi: 10.1038/nchembio.671.
8
Combinatorial biosynthesis in plants: a (p)review on its potential and future exploitation.植物中的组合生物合成：潜力及其未来开发的综述。
Nat Prod Rep. 2011 Nov;28(12):1897-916. doi: 10.1039/c1np00049g. Epub 2011 Sep 28.
9
Natural products and Pharma 2011: strategic changes spur new opportunities.天然产物与制药 2011：战略变革催生新机遇。
Nat Prod Rep. 2011 Oct;28(11):1783-9. doi: 10.1039/c1np00033k. Epub 2011 Sep 12.
10
Enzymatic methods for glyco(diversification/randomization) of drugs and small molecules.酶法用于药物和小分子的糖基（多样化/随机化）。
Nat Prod Rep. 2011 Oct;28(11):1811-53. doi: 10.1039/c1np00045d. Epub 2011 Sep 8.
Zotero 插件