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Open Access Article

International Medical Research Frontier. 2024; 8: (1) ; 21-24 ; DOI: 10.12208/j.imrf.20240005.

Progress in biosynthesis and enzyme engineering of natural products
天然产物的生物合成及酶工程研究进展

作者: 谭彩玲, 张剑, 余伯阳 *

中国药科大学 江苏南京

*通讯作者: 余伯阳,单位:中国药科大学 江苏南京;

发布时间: 2024-06-28 总浏览量: 119

摘要

天然产物是动物、植物、微生物来源的特殊代谢产物,为药物研发提供了重要来源。因其绿色、可持续的特点,天然产物的生物合成具有广阔的应用前景,其主要程序包括底盘细胞的确认,代谢途径的设计,发酵工艺的放大。酶作为天然产物生物合成的催化剂,通常不完全具备目标产物合成的所需特性,需对其进行酶工程改造。这些酶工程策略包括定向进化、理性设计、半理性设计,以提升酶特性从而适应于天然产物的生物合成应用。

关键词: 天然产物;生物合成;酶工程

Abstract

Natural products are special metabolites from animals, plants and microorganisms, which provide an important source for drug research and development. Because of its green and sustainable characteristics, the biosynthesis of natural products has broad application prospects. The main procedures include the identification of chassis cells, the design of metabolic pathways, and the amplification of fermentation processes. As catalysts for natural product biosynthesis, enzymes usually do not have the required properties of target product synthesis, so they need to be modified by enzyme engineering. These enzyme engineering strategies include directed evolution, rational design, and semi-rational design to improve enzyme properties for biosynthetic applications of natural products.

Key words: Natural products; Biosynthesis; Enzyme engineering

参考文献 References

[1] Elshafie H S, Camele I, Mohamed A A. A Comprehensive Review on the Biological, Agricultural and Pharmaceutical Properties of Secondary Metabolites Based-Plant Origin[J]. Int J Mol Sci,2023,24(4).

[2] Atanasov A G, Zotchev S B, Dirsch V M, et al. Natural products in drug discovery: advances and opportunities[J]. Nat Rev Drug Discov,2021,20(3):200-216.

[3] Li G, Lou H X. Strategies to diversify natural products for drug discovery[J]. Med Res Rev,2018,38(4):1255-1294.

[4] Kelwick R, Macdonald J T, Webb A J, et al. Developments in the tools and methodologies of synthetic biology[J]. Front Bioeng Biotechnol,2014,2:60.

[5] Yang D, Park S Y, Park Y S, et al. Metabolic Engineering of Escherichia coli for Natural Product Biosynthesis[J]. Trends Biotechnol,2020,38(7):745-765.

[6] Paddon C J, Westfall P J, Pitera D J, et al. High-level semi-synthetic production of the potent antimalarial artemisinin[J]. Nature,2013,496(7446):528.

[7] Ajikumar P K, Xiao W H, Tyo K E, et al. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia  coli[J]. Science,2010,330(6000):70-74.

[8] Galanie S, Thodey K, Trenchard I J, et al. Complete biosynthesis of opioids in yeast[J]. Science,2015,349(6252): 1095-1100.

[9] Tan Z, Li J, Hou J, et al. Designing artificial pathways for improving chemical production[J]. Biotechnol Adv,2023,64: 108119.

[10] Ganeshan S, Kim S H, Vujanovic V. Scaling-up production of plant endophytes in bioreactors: concepts, challenges  and perspectives[J]. Bioresour Bioprocess,2021,8(1):63.

[11] Xia J, Wang G, Lin J, et al. Advances and Practices of Bioprocess Scale-up[J]. Adv Biochem Eng Biotechnol,2016, 152: 137-151.

[12] 夏建业,刘晶,庄英萍. 人工智能时代发酵优化与放大技术的机遇与挑战[J]. 生物工程学报,2022,38(11):4180-4199.

[13] Shoda S, Uyama H, Kadokawa J, et al. Enzymes as Green Catalysts for Precision Macromolecular Synthesis[J]. Chem Rev,2016,116(4):2307-2413.

[14] Victorino D S A I, Gonsales D R N, Antonio D O S F, et al. Enzyme engineering and its industrial applications[J]. Biotechnol Appl Biochem,2022,69(2):389-409.

[15] Arnold F H. Innovation by Evolution: Bringing New Chemistry to Life (Nobel Lecture)[J]. Angew Chem Int Ed Engl, 2019,58(41):14420-14426.

[16] Zeymer C, Hilvert D. Directed Evolution of Protein Catalysts[J]. Annu Rev Biochem,2018,87:131-157.

[17] Wang Y, Xue P, Cao M, et al. Directed Evolution: Methodologies and Applications[J]. Chem Rev,2021,121(20): 12384-12444.

[18] Markel U, Essani K D, Besirlioglu V, et al. Advances in ultrahigh-throughput screening for directed enzyme evolution [J]. Chem Soc Rev,2020,49(1):233-262.

[19] Xu S Y, Zhou L, Xu Y, et al. Recent advances in structure-based enzyme engineering for functional  reconstruction[J]. Biotechnol Bioeng,2023,120(12):3427-3445.

[20] Ding Y, Perez-Ortiz G, Peate J, et al. Redesigning Enzymes for Biocatalysis: Exploiting Structural Understanding for  Improved Selectivity[J]. Front Mol Biosci,2022,9:908285.

[21] Chica R A, Doucet N, Pelletier J N. Semi-rational approaches to engineering enzyme activity: combining the benefits  of directed evolution and rational design[J]. Curr Opin Biotechnol, 2005,16(4):378-384.

[22] Phintha A, Chaiyen P. Rational and mechanistic approaches for improving biocatalyst performance,[J]. Chem Catal,2022, 2(10):2614-2643.

引用本文

谭彩玲, 张剑, 余伯阳, 天然产物的生物合成及酶工程研究进展[J]. 国际医药研究前沿, 2024; 8: (1) : 21-24.