
Recent advances of natural product pesticide milbemycins from Streptomyces
Xue Yang, Guozhong Du, Xiaojin Li, Wensheng Xiang, Shanshan Li, Yanyan Zhang
New Plant Protection ›› 2024, Vol. 1 ›› Issue (2) : e18.
Recent advances of natural product pesticide milbemycins from Streptomyces
Milbemycins are a group of 16-membered macrolides produced by the soil-dwelling filamentous bacteria Streptomyces. Renowned for their potent acaricidal and insecticidal properties, combined with low toxicity, milbemycins are recognized as eco-friendly biopesticides, vital for pest control and sustainable agricultural development. Over several decades, milbemycins have been extensively investigated, achieving significant progress, including advancements in their biological activities (such as insecticidal mechanisms and toxicity studies), biosynthetic and regulatory mechanisms, high-yield strain engineering strategies, and the development of milbemycin-derived commercial products for agricultural applications. This review discusses recent advances, current limitations, and ongoing and emerging efforts to overcome the limitations of milbemycin research. Finally, future research directions are outlined for the development of superior milbemycin-producing cell factories to facilitate widespread application in the agricultural field.
biopesticide / biosynthesis and regulation / engineered microorganism / milbemycins / streptomyces / synthetic biology
[1] |
FAO (UN Food Agric. Organ.). (2009). Global agriculture towards 2050. In High Level Expert Forum. FAO.
|
[2] |
Douglas, A. E. (2018). Strategies for enhanced crop resistance to insect pests. Annual Review of Plant Biology, 69(1), 637–660.
CrossRef
Google scholar
|
[3] |
Popp, J., Pető, K., & Nagy, J. (2013). Pesticide productivity and food security. A review. Agronomy for Sustainable Development, 33(1), 243–255.
CrossRef
Google scholar
|
[4] |
Budzinski, H., & Couderchet, M. (2018). Environmental and human health issues related to pesticides: From usage and environmental fate to impact. Environmental Science and Pollution Research, 25(15), 14277–14279.
CrossRef
Google scholar
|
[5] |
Shen, J., Zhu, Q., Jiao, X., Ying, H., Wang, H., Wen, X., Xu, W., Li, T., Cong, W., Liu, X., Hou, Y., Cui, Z., Oenema, O., Davies, W. J., & Zhang, F. (2020). Agriculture green development: A model for China and the world. Frontiers of Agricultural Science and Engineering, 7(1), 5–13.
CrossRef
Google scholar
|
[6] |
Song, R., Zhang, Y., Lu, P., Wu, J., Li, Q. X., & Song, B. (2024). Status and perspective on green pesticide utilizations and food security. Annual Review of Food Science and Technology, 15(1), 473–493.
CrossRef
Google scholar
|
[7] |
Dayan, F. E., Cantrell, C. L., & Duke, S. O. (2009). Natural products in crop protection. Bioorganic and Medicinal Chemistry, 17(2), 4022–4034.
CrossRef
Google scholar
|
[8] |
Kenshole, E., Herisse, M., Michael, M., & Pidot, S. J. (2021). Natural product discovery through microbial genome mining. Current Opinion in Chemical Biology, 60, 47–54.
CrossRef
Google scholar
|
[9] |
Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E. M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E. H., Rollinger, J. M., Schuster, D., Breuss, J. M., Bochkov, V., Mihovilovic, M. D., Kopp, B., Bauer, R., Dirsch, V. M., & Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33(8), 1582–1614.
CrossRef
Google scholar
|
[10] |
Cui, J., & Zhang, X. (2021). Development and high yield strategies of microbial-derived antibiotics in agriculture. Chinese Journal of Biotechnology, 37(3), 1032–1041. https://doi.org/10.13345/j.cjb.200643
|
[11] |
Tan, H. (2022). Review and prospect of biological pesticides in China. World Pesticide, 44, 16–27. https://doi.org/10.16201/j.cnki.cn10-1660/tq.2022.04.03
|
[12] |
Li, S., Li, Z., Tan, G. Y., Xin, Z., & Wang, W. (2023). In vitro allosteric transcription factor-based biosensing. Trends in Biotechnology, 41(8), 1080–1095.
CrossRef
Google scholar
|
[13] |
Arnold, A., Alexander, J., Liu, G., & Stokes, J. M. (2023). Applications of machine learning in microbial natural product drug discovery. Expert Opinion on Drug Discovery, 18(11), 1259–1272.
CrossRef
Google scholar
|
[14] |
Katz, L., & Baltz, R. H. (2016). Natural product discovery: Past, present, and future. Journal of Industrial Microbiology and Biotechnology, 43(2–3), 155–176.
CrossRef
Google scholar
|
[15] |
Yan, Y. S., & Xia, H. Y. (2021). Recent advances in the research of milbemycin biosynthesis and regulation as well as strategies for strain improvement. Archives of Microbiology, 203(10), 5849–5857.
CrossRef
Google scholar
|
[16] |
McKellar, Q. A., & Benchaoui, H. A. (1996). Avermectins and milbemycins. Journal of Veterinary Pharmacology and Therapeutics, 19(5), 331–351.
CrossRef
Google scholar
|
[17] |
Wang, X. J., Zhang, B., Yan, Y. J., An, J., Zhang, J., Liu, C. X., & Xiang, W. S. (2013). Characterization and analysis of an industrial strain of Streptomyces bingchenggensis by genome sequencing and gene microarray. Genome, 56(11), 677–689.
CrossRef
Google scholar
|
[18] |
Ono, M., Mishima, H., Takiguchi, Y., Terao, M., Kobayashi, H., Iwasaki, S., & Okuda, S. (1983). Milbemycins, a new family of macrolide antibiotics. Studies on the biosynthesis of milbemycins a2, a4 and D using 13C labeled precursors. Journal of Antibiotics, 36(8), 991–1000.
CrossRef
Google scholar
|
[19] |
Takiguchi, Y., Mishima, H., Okuda, M., Terao, M., Aoki, A., & Fukuda, R. (1980). Milbemycins, a new family of macrolide antibiotics: Fermentation, isolation and physico-chemical properties. Journal of Antibiotics, 33(10), 1120–1127.
CrossRef
Google scholar
|
[20] |
Nonaka, K., Kumasaka, C., Okamoto, Y., Maruyama, F., & Yoshikawa, H. (1999). Bioconversion of milbemycin-related compounds: Biosynthetic pathway of milbemycins. Journal of Antibiotics, 52(2), 109–116.
CrossRef
Google scholar
|
[21] |
Tsukiyama, T., Kinoshita, A., Ichinose, R., & Sato, K. (2003). Milbemycin a17 and related compounds synthesized from milbemycin A4: Synthetic procedure and acaricidal activities. Journal of Antibiotics, 56(10), 848–855.
CrossRef
Google scholar
|
[22] |
Chu, L., Li, S., Dong, Z., Zhang, Y., Jin, P., Ye, L., Wang, X., & Xiang, W. (2022). Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces. Microbial Biotechnology, 15(4), 1120–1132.
CrossRef
Google scholar
|
[23] |
Zhang, Y., He, H., Liu, H., Wang, H., Wang, X., & Xiang, W. (2016). Characterization of a pathway-specific activator of milbemycin biosynthesis and improved milbemycin production by its overexpression in Streptomyces bingchenggensis. Microbial Cell Factories, 15(1), 152.
CrossRef
Google scholar
|
[24] |
Wolstenholme, A. J., & Rogers, A. T. (2005). Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology, 131(Suppl), S85–S95.
CrossRef
Google scholar
|
[25] |
Shoop, W. L., Mrozik, H., & Fisher, M. H. (1995). Structure and activity of avermectins and milbemycins in animal health. Veterinary Parasitology, 59(2), 139–156.
CrossRef
Google scholar
|
[26] |
Zhang, B., Wang, X., & Xiang, W. (2009). Advance in toxicological research of milbemectin. World Pesticide, 31(4), 11–12.49. https://doi.org/10.3969/j.issn.1009-6485.2009.04.003
|
[27] |
Hu, H., Zhu, B., & Li, J. (2000). Progress in research of avermectins. Acta Veterinaria et Zootechnica Sinica, 31(6), 520–529. https://doi.org/10.3321/j.issn:0366-6964.2000.06.008
|
[28] |
Wang, Z., Wang, X., & Xiang, W. (2009). Review of insecticidal activity characteristics of the biopesticide milbemycin. World Pesticide, 31(1), 13–15. https://doi.org/10.3969/j.issn.1009-6485.2009.01.004
|
[29] |
Mishima, H., Ide, J., Muramatsu, S., & Ono, M. (1983). Milbemycins, a new family of macrolide antibiotics. Structure determination of milbemycins D, E, F, G, H, J and K. Journal of Antibiotics, 36(8), 980–990.
CrossRef
Google scholar
|
[30] |
Xia, G., Liu, C., Wang, X., & Xiang, W. (2012). The application of biological pesticide milbemycin. World Pesticide, 34(3), 35–39. https://doi.org/10.3969/j.issn.1009-6485.2012.03.009
|
[31] |
Takahashi, S., Miyaoka, H., Tanaka, K., Enokita, R., & Okazaki, T. (1993). Milbemycins a11, a12, a13, a14 and a15: A new family of milbemycins from Streptomyces hygroscopicus subsp. aureolacrimosus taxonomy, fermentation, isolation, structure elucidation and biological properties. Journal of Antibiotics, 46(9), 1364–1371.
CrossRef
Google scholar
|
[32] |
Hao, Z. K., Zhang, S. Y., Qi, H., Xiang, W. S., Li, J. S., & Wang, J. D. (2023). A novel spiro-heterocycle milbemycin metabolite from a genetically engineered strain of Streptomyces bingchenggensis. Natural Product Research, 37(3), 449–454.
CrossRef
Google scholar
|
[33] |
Tan, G. Y., & Liu, T. (2017). Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria. Metabolic Engineering, 39, 228–236.
CrossRef
Google scholar
|
[34] |
Wang, X. J., Yan, Y. J., Zhang, B., An, J., Wang, J. J., Tian, J., Jiang, L., Chen, Y. H., Huang, S. X., Yin, M., Zhang, J., Gao, A. L., Liu, C. X., Zhu, Z. X., & Xiang, W. S. (2010). Genome sequence of the milbemycin-producing bacterium Streptomyces bingchenggensis. Journal of Bacteriology, 192(17), 4526–4527.
CrossRef
Google scholar
|
[35] |
He, Y., Sun, Y., Liu, T., Zhou, X., Bai, L., & Deng, Z. (2010). Cloning of separate meilingmycin biosynthesis gene clusters by use of acyltransferase-ketoreductase didomain PCR amplification. Applied and Environmental Microbiology, 76(10), 3283–3292.
CrossRef
Google scholar
|
[36] |
Ikeda, H., Nonomiya, T., Usami, M., Ohta, T., & Omura, S. (1999). Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis. Proceedings of the National Academy of Sciences of the United States of America, 96(17), 9509–9514.
CrossRef
Google scholar
|
[37] |
Ikeda, H., & Omura, S. (1997). Avermectin biosynthesis. Chemical Reviews, 97(7), 2591–2610.
CrossRef
Google scholar
|
[38] |
Wang, H., Cheng, X., Liu, Y., Li, S., Zhang, Y., Wang, X., & Xiang, W. (2020). Improved milbemycin production by engineering two Cytochromes P450 in Streptomyces bingchenggensis. Applied Microbiology and Biotechnology, 104(7), 2935–2946.
CrossRef
Google scholar
|
[39] |
Wang, H. Y., Zhang, J., Zhang, Y. J., Zhang, B., Liu, C. X., He, H. R., Wang, X. J., & Xiang, W. S. (2014). Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces bingchenggensis. Applied Microbiology and Biotechnology, 98(23), 9703–9712.
CrossRef
Google scholar
|
[40] |
Zhang, J., An, J., Wang, J. J., Yan, Y. J., He, H. R., Wang, X. J., & Xiang, W. S. (2013). Genetic engineering of Streptomyces bingchenggensis to produce milbemycins A3/A4 as main components and eliminate the biosynthesis of nanchangmycin. Applied Microbiology and Biotechnology, 97(23), 10091–10101.
CrossRef
Google scholar
|
[41] |
Wang, X. J., Wang, C. Q., Sun, X. L., & Xiang, W. S. (2010). 5-ketoreductase from Streptomyces bingchengensis: Overexpression and preliminary characterization. Biotechnology Letters, 32(10), 1497–1502.
CrossRef
Google scholar
|
[42] |
Sun, P., Zhao, Q., Yu, F., Zhang, H., Wu, Z., Wang, Y., Wang, Y., Zhang, Q., & Liu, W. (2013). Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC. Journal of the American Chemical Society, 135(4), 1540–1548.
CrossRef
Google scholar
|
[43] |
Deng, C., Wu, Y., Lv, X., Li, J., Liu, Y., Du, G., Chen, J., & Liu, L. (2022). Refactoring transcription factors for metabolic engineering. Biotechnology Advances, 57, 107935.
CrossRef
Google scholar
|
[44] |
Liu, G., Chater, K. F., Chandra, G., Niu, G., & Tan, H. (2013). Molecular regulation of antibiotic biosynthesis in streptomyces. Microbiology and Molecular Biology Reviews, 77(1), 112–143.
CrossRef
Google scholar
|
[45] |
Laing, E., Sidhu, K., & Hubbard, S. J. (2008). Predicted transcription factor binding sites as predictors of operons in Escherichia coli and Streptomyces coelicolor. BMC Genomics, 9(1), 79.
CrossRef
Google scholar
|
[46] |
Romero-Rodríguez, A., Robledo-Casados, I., & Sánchez, S. (2015). An overview on transcriptional regulators in Streptomyces. Biochimica et Biophysica Acta, 1849(8), 1017–1039.
CrossRef
Google scholar
|
[47] |
Liu, H., Zhang, Y., Li, S., Wang, J., Wang, X., & Xiang, W. (2020). Elucidation of the activation pathways of ScyA1/ScyR1, an aco/ArpA-like system that regulates the expression of nemadectin and other secondary metabolic biosynthetic genes. Frontiers in Bioengineering and Biotechnology, 8, 589730.
CrossRef
Google scholar
|
[48] |
Zhou, Q., Ning, S., & Luo, Y. (2020). Coordinated regulation for nature products discovery and overproduction in Streptomyces. Synthetic and Systems Biotechnology, 5(2), 49–58.
CrossRef
Google scholar
|
[49] |
Wei, K., Wu, Y., Li, L., Jiang, W., Hu, J., Lu, Y., & Chen, S. (2018). MilR2, a novel TetR family regulator involved in 5-oxomilbemycin A3/A4 biosynthesis in Streptomyces hygroscopicus. Applied Microbiology and Biotechnology, 102(20), 8841–8853.
CrossRef
Google scholar
|
[50] |
Yan, Y. S., Yang, Y. Q., Zhou, L. S., Zhang, L., & Xia, H. Y. (2022). MilR3, a unique SARP family pleiotropic regulator in Streptomyces bingchenggensis. Archives of Microbiology, 204(10), 631.
CrossRef
Google scholar
|
[51] |
Wang, H., Liu, Y., Cheng, X., Zhang, Y., Li, S., Wang, X., & Xiang, W. (2022). Titer improvement of milbemycins via coordinating metabolic competition and transcriptional co-activation controlled by Streptomyces antibiotic regulatory protein family regulator in Streptomyces bingchenggensis. Biotechnology and Bioengineering, 119(5), 1252–1263.
CrossRef
Google scholar
|
[52] |
Yan, Y. S., Zou, L. S., Wei, H. G., Yang, M. Y., Yang, Y. Q., Li, X. F., & Xia, H. Y. (2024). An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in Streptomyces bingchenggensis. Applied and Environmental Microbiology, 90(1), e0130023.
CrossRef
Google scholar
|
[53] |
He, H., Ye, L., Li, C., Wang, H., Guo, X., Wang, X., Zhang, Y., & Xiang, W. (2018). SbbR/SbbA, an important ArpA/AfsA-Like system, regulates milbemycin production in Streptomyces bingchenggensis. Frontiers in Microbiology, 9, 1064.
CrossRef
Google scholar
|
[54] |
Zhu, Y., Wang, J., Li, S., Xiang, W., & Zhang, Y. (2023). Effect of the global regulator MtrAsbh on the biosynthesis of milbemycins. Chinese Journal of Biological Control, 39(5), 1083–1093. https://doi.org/10.16409/j.cnki.2095-039x.2022.03.030
|
[55] |
Ye, L., Zhang, Y., Li, S., He, H., Ai, G., Wang, X., & Xiang, W. (2022). Transcriptome-guided identification of a four-component system, SbrH1-R, that modulates milbemycin biosynthesis by influencing gene cluster expression, precursor supply, and antibiotic efflux. Synthetic and Systems Biotechnology, 7(2), 705–717.
CrossRef
Google scholar
|
[56] |
Yang, X., Zhang, Y., Li, S., Ye, L., Wang, X., & Xiang, W. (2022). SspH, a novel HATPase family regulator, controls antibiotic biosynthesis in streptomyces. Antibiotics, 11(5), 538.
CrossRef
Google scholar
|
[57] |
Wang, X., Wang, X., & Xiang, W. (2009). Improvement of milbemycin-producing Streptomyces bingchenggensis by rational screening of ultraviolet- and chemically induced mutants. World Journal of Microbiology and Biotechnology, 25(6), 1051–1056.
CrossRef
Google scholar
|
[58] |
Li, L., Wei, K., Liu, X., Wu, Y., Zheng, G., Chen, S., Jiang, W., & Lu, Y. (2019). aMSGE: advanced multiplex site-specific genome engineering with orthogonal modular recombinases in actinomycetes. Metabolic Engineering, 52, 153–167.
CrossRef
Google scholar
|
[59] |
Teijaro, C. N., Adhikari, A., & Shen, B. (2019). Challenges and opportunities for natural product discovery, production, and engineering in native producers versus heterologous hosts. Journal of Industrial Microbiology and Biotechnology, 46(3–4), 433–444.
CrossRef
Google scholar
|
[60] |
Xue, C., Duan, Y., Zhao, F., & Lu, W. (2013). Stepwise increase of spinosad production in Saccharopolyspora spinosa by metabolic engineering. Biochemical Engineering Journal, 72, 90–95.
CrossRef
Google scholar
|
[61] |
Jiang, H., Wang, Y. Y., Ran, X. X., Fan, W. M., Jiang, X. H., Guan, W. J., & Li, Y. Q. (2013). Improvement of natamycin production by engineering of phosphopantetheinyl transferases in Streptomyces chattanoogensis L10. Applied and Environmental Microbiology, 79(11), 3346–3354.
CrossRef
Google scholar
|
[62] |
Miao, V., Coëffet-LeGal, M. F., Brian, P., Brost, R., Penn, J., Whiting, A., Martin, S., Ford, R., Parr, I., Bouchard, M., Silva, C. J., Wrigley, S. K., & Baltz, R. H. (2005). Daptomycin biosynthesis in Streptomyces roseosporus: Cloning and analysis of the gene cluster and revision of peptide stereochemistry. Microbiology, 151(5), 1507–1523.
CrossRef
Google scholar
|
[63] |
Weber, T., Charusanti, P., Musiol-Kroll, E. M., Jiang, X., Tong, Y., Kim, H. U., & Lee, S. Y. (2015). Metabolic engineering of antibiotic factories: New tools for antibiotic production in actinomycetes. Trends in Biotechnology, 33(1), 15–26.
CrossRef
Google scholar
|
[64] |
Olano, C., Méndez, C., & Salas, J. A. (2010). Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis. Natural Product Reports, 27(4), 571–616.
CrossRef
Google scholar
|
[65] |
Rinaldi, L., Pennacchio, S., Musella, V., Maurelli, M. P., Torre, L. F., & Cringoli, G. (2015). Helminth control in kennels: Is the combination of milbemycin oxime and praziquantel a right choice? Parasites and Vectors, 8(1), 30.
CrossRef
Google scholar
|
[66] |
McCall, J. W. (2005). The safety-net story about macrocyclic lactone heartworm preventives: A review, an update, and recommendations. Veterinary Parasitology, 133(2–3), 197–206.
CrossRef
Google scholar
|
[67] |
Li, X., Yan, Y., Xie, S., Li, Z., & Xia, H. (2023). Enhancement of milbemycins production by phosphopantetheinyl transferase and regulatory pathway engineering in Streptomyces bingchenggensis. World Journal of Microbiology and Biotechnology, 39(10), 278.
CrossRef
Google scholar
|
[68] |
Xu, X., Li, X., Liu, Y., Zhu, Y., Li, J., Du, G., Chen, J., Ledesma-Amaro, R., & Liu, L. (2020). Pyruvate-responsive genetic circuits for dynamic control of central metabolism. Nature Chemical Biology, 16(11), 1261–1268.
CrossRef
Google scholar
|
[69] |
Qiu, X., Xu, P., Zhao, X., Du, G., Zhang, J., & Li, J. (2020). Combining genetically-encoded biosensors with high throughput strain screening to maximize erythritol production in Yarrowia lipolytica. Metabolic Engineering, 60, 66–76.
CrossRef
Google scholar
|
[70] |
Li, Y. P., Yu, P., Li, J. F., Tang, Y. L., Bu, Q. T., Mao, X. M., & Li, Y. Q. (2019). FadR1, a pathway-specific activator of fidaxomicin biosynthesis in Actinoplanes deccanensis Yp-1. Applied Microbiology and Biotechnology, 103(18), 7583–7596.
CrossRef
Google scholar
|
[71] |
Wang, W., Li, S., Li, Z., Zhang, J., Fan, K., Tan, G., Ai, G., Lam, S. M., Shui, G., Yang, Z., Lu, H., Jin, P., Li, Y., Chen, X., Xia, X., Liu, X., Dannelly, H. K., Yang, C., Yang, Y., … Zhang, L. (2020). Harnessing the intracellular triacylglycerols for titer improvement of polyketides in Streptomyces. Nature Biotechnology, 38(1), 76–83.
CrossRef
Google scholar
|
[72] |
Yang, X., Jin, P., Dong, Z., Zhang, Y., Xiang, W., & Li, S. (2023). Optimization of milbemycin component ratio by coordinating acyl-coenzyme A supply pathways in Streptomyces bingchenggensis. Fermentation, 9(6), 555.
CrossRef
Google scholar
|
[73] |
Li, S., Li, Z., Pang, S., Xiang, W., & Wang, W. (2021). Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces. Current Opinion in Biotechnology, 69, 26–34.
CrossRef
Google scholar
|
[74] |
Lu, C., Zhang, X., Jiang, M., & Bai, L. (2016). Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus. Metabolic Engineering, 35, 129–137.
CrossRef
Google scholar
|
[75] |
Liu, Y., Wang, H., Li, S., Zhang, Y., Cheng, X., Xiang, W., & Wang, X. (2021). Engineering of primary metabolic pathways for titer improvement of milbemycins in Streptomyces bingchenggensis. Applied Microbiology and Biotechnology, 105(5), 1875–1887.
CrossRef
Google scholar
|
[76] |
Kim, M. S., Choc, W. J., Song, M. C., Park, S. W., Kim, K., Kim, E., Lee, N., Nam, S. J., Oh, K. H., & Yoon, Y. J. (2017). Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis. Microbial Cell Factories, 16(1), 9.
CrossRef
Google scholar
|
[77] |
Zhu, Y., Zhou, C., Wang, Y., & Li, C. (2020). Transporter engineering for microbial manufacturing. Biotechnology Journal, 15(9), e1900494.
CrossRef
Google scholar
|
[78] |
Jin, P., Li, S., Zhang, Y., Chu, L., He, H., Dong, Z., & Xiang, W. (2020). Mining and fine-tuning sugar uptake system for titer improvement of milbemycins in Streptomyces bingchenggensis. Synthetic and Systems Biotechnology, 5(3), 214–221.
CrossRef
Google scholar
|
[79] |
Dong, Z., Li, L., Du, G., Zhang, Y., Wang, X., Li, S., & Xiang, W. (2024). A previously unidentified sugar transporter for engineering of high-yield Streptomyces. Applied Microbiology and Biotechnology, 108(1), 72.
CrossRef
Google scholar
|
[80] |
Henson, M. A. (2015). Genome-scale modelling of microbial metabolism with temporal and spatial resolution. Biochemical Society Transactions, 43(6), 1164–1171.
CrossRef
Google scholar
|
[81] |
Choi, K. R., Jang, W. D., Yang, D., Cho, J. S., Park, D., & Lee, S. Y. (2019). Systems metabolic engineering strategies: Integrating systems and synthetic biology with metabolic engineering. Trends in Biotechnology, 37(8), 817–837.
CrossRef
Google scholar
|
[82] |
Shis, D. L., Bennett, M. R., & Igoshin, O. A. (2018). Dynamics of bacterial gene regulatory networks. Annual Review of Biophysics, 47(1), 447–467.
CrossRef
Google scholar
|
[83] |
Lou, C., Stanton, B., Chen, Y. J., Munsky, B., & Voigt, C. A. (2012). Ribozyme-based insulator parts buffer synthetic circuits from genetic context. Nature Biotechnology, 30(11), 1137–1142.
CrossRef
Google scholar
|
[84] |
Li, J., Mu, X., Dong, W., Chen, Y., Kang, Q., Zhao, G., Hou, J., Gonzalez, R., Bai, L., Feng, Y., Yang, C., Liu, T., & Tan, Z. (2024). A non-carboxylative route for the efficient synthesis of central metabolite malonyl-CoA and its derived products. Nature catalysis, 7(4), 361–374.
CrossRef
Google scholar
|
[85] |
Ren, S., Sun, Q., Zhang,
CrossRef
Google scholar
|
[86] |
Zhou, H., Zhang, C., Li, Z., Xia, M., Li, Z., Wang, Z., Tan, G. Y., Luo, Y., Zhang, L., & Wang, W. (2024). Systematic development of a highly efficient cell factory for 5-aminolevulinic acid production. Trends in Biotechnology, 42(11), 1479–1502.
CrossRef
Google scholar
|
[87] |
Cui, Y., Chen, Y., Liu, X., Dong, S., Tian, Y., Qiao, R., Mitra, R., Han, J., Li, C., Han, X., Liu, W., Chen, Q., Wei, W., Wang, X., Du, W., Tang, S., Xiang, H., Liu, H., Liang, Y., Houk, K. N., & Wu, B. (2021). Computational redesign of a PETase for plastic biodegradation under ambient condition by the GRAPE strategy. ACS Catalysis, 11(3), 1340–1350.
CrossRef
Google scholar
|
[88] |
Cui, Y., Chen, Y., Sun, J., Zhu, T., Pang, H., Li, C., Geng, W. C., & Wu, B. (2024). Computational redesign of a hydrolase for nearly complete PET depolymerization at industrially relevant high-solids loading. Nature Communications, 15(1), 1417.
CrossRef
Google scholar
|
[89] |
Zhang, P., Wang, H., Xu, H., Wei, L., Liu, L., Hu, Z., & Wang, X. (2023). Deep flanking sequence engineering for efficient promoter design using DeepSEED. Nature Communications, 14(1), 6309.
CrossRef
Google scholar
|
/
〈 |
|
〉 |