Research Progress in Biosynthesis of Secondary Metabolites of Microorganisms

doi:10.13560/j.cnki.biotech.bull.1985.2020-0475

Abstract

Abstract:

Microorganisms can produce a variety of natural secondary metabolites with biological activity,which have broad application prospects in medical,agricultural and food fields. The development of molecular biology, bioinformatics and sequencing technology has laid a theoretical foundation for the mining of secondary metabolites and provided operational tools. In recent years,there are more and more studies on the secondary metabolites of microorganisms. It is difficult to get satisfactory results by traditional methods. It will be a new direction to operate microorganisms at the molecular level,such as the regulation of secondary metabolite biosynthesis gene cluster.The strategies of finding new secondary metabolites and increasing the production of secondary metabolites were reviewed,by using the methods of heterologous expression of secondary metabolite biosynthesis gene cluster,ribosome engineering,epigenetic regulation,metabolic regulation and regulation of transcription and translation level,the aim is to excavate new secondary metabolites,improve the production of secondary metabolites,and provide a breakthrough for the exploration of new drugs.

Key words: secondary metabolites, biosynthetic gene clusters, heterologous expression

ZHAO Jiang-hua, FANG Huan, ZHANG Da-wei. Research Progress in Biosynthesis of Secondary Metabolites of Microorganisms[J]. Biotechnology Bulletin, 2020, 36(11): 141-147.

References 40

[1]	周豪. 限制修饰缺失大肠杆菌的构建及其在微生物次级代谢研究中的应用[D]. 上海:上海交通大学, 2011.
	Zhou H. Non-restricting and methylation deficient Escherichia coli strains for bacterial secondary metabolism research[D]. Shanghai:Shanghai Jiao Tong University, 2011.
[2]	刘志恒, 姜成林. 放线菌现代生物学与生物技术[M]. 北京: 科学出版社, 2004.
	Liu ZH, Jiang CL. Modern biology and biotechnology of actinomycetes[M]. Beijing: Science Press, 2004.
[3]	孙天拥. 细菌界次级代谢产物生物合成基因簇的基因组学注释和比较研究[D]. 济南:山东大学, 2016.
	Sun TY. Genomics annotation and comparative studies of secondary metabolite biosynthetic gene clusters of the kingdom Bacteria[D]. Jinan:Shandong University, 2016.
[4]	Hug JJ, Krug D, Müller R. Bacteria as genetically programmable producers of bioactive natural products[J]. Nature Reviews Chemistry, 2020,4(4):172-193. doi: 10.1038/s41570-020-0176-1 URL
[5]	赵婷峰, 龚国利. 黏细菌:天然的制药厂[J]. 生物技术通报, 2014(12):40-46. doi: 10.13560/j.cnki.biotech.bull.1985.2014.12.007 URL
	Zhao TF, Gong GL. Myxobacteria:Natural pharmaceutical factories[J]. Biotechnology Bulletin, 2014(12):40-46. doi: 10.13560/j.cnki.biotech.bull.1985.2014.12.007 URL
[6]	Berdy J. Bioactive microbial metabolites[J]. The Journal of Antibiotics(Tokyo), 2005,58(1):1-26.
[7]	Woloshuk CP, Shim WB. Aflatoxins, fumonisins, andtrichothecenes:a convergence of knowledge[J]. FEMS Microbiology Reviews, 2013,37:94-109. doi: 10.1111/1574-6976.12009 URL pmid: 23078349
[8]	潘圆圆, 李二伟, 车永胜, 等. 丝状真菌次级代谢产物的研究现状与发展趋势[J]. 菌物学报, 2015,34(5):890-899.
	Pan YY, Li EW, Che YS, et al. Research progresses and trends of secondary metabolites in filamentous fungi[J]. Mycosystema, 2015,34(5):890-899.
[9]	张超群, 戴建荣. 放线菌的研究现况与展望[J]. 中国病原生物学杂志, 2019,14(1):110-113.
	Zhang CQ, Dai JR. Status of and prospects for research on actinomycetes[J]. Journal of Pathogen Biology, 2019,14(1):110-113.
[10]	Wohlleben W, Mast Y, Muth G, et al. Synthetic biology of secondary metabolite biosynjournal in actinom ycetes:Engineering precursor supply as a way to optimize antibiotic production[J]. FEBS Letters, 2012,586(15):2171-2176. doi: 10.1016/j.febslet.2012.04.025 URL pmid: 22710162
[11]	Yin J, Straight PD, Hrvatin S, et al. Genome-wide high-through put mining of natural-product biosynthetic gene clusters by phage display[J]. Chem Biol, 2007,14(3):303-312. doi: 10.1016/j.chembiol.2007.01.006 URL pmid: 17379145
[12]	Ochi K, Hosaka T. New strategies for drug discovery:activation of silent or weakly expressed microbial gene clusters[J]. Appl Microbiol Biotech, 2013,97(1):87-98.
[13]	Nielsen MR, Wollenberg RD, Westphal K, et al. RingsborgHeterologous expression of intact biosynthetic gene clusters in Fusarium graminearum[J]. Fungal Genetics and Biology, 2019,132:103-248.
[14]	Harvey CJ, Tang M, Schlecht U, et al. HEx:A heterologous expression platform for the discovery of fungal natural products[J]. Sci Adv, 2018, 4(4):eaar 5459.
[15]	He Y, Wang B, Chen WP. Recent advances in reconstructing microbial secondary metabolites biosynjournal in Aspergillus spp[J]. Biotechnology Advances, 2018,36:739-783. doi: 10.1016/j.biotechadv.2018.02.001 URL pmid: 29421302
[16]	Kjærbølling I, Mortensen UH, Vesth T, Andersen MR. Strategies to establish the link between biosynthetic gene clusters and secondary metabolites[J]. Fungal Genetics and Biology, 2019,130:107-121. doi: 10.1016/j.fgb.2019.06.001 URL pmid: 31195124
[17]	童瑞年, 吴旭日, 陈依军. TAR 克隆技术及其在微生物次级代谢产物研究中的应用[J]. 中国药科大学学报, 2018,49(2):129-135.
	Tong RN, Wu XR, Chen YJ. Application of TAR cloning in microbial secondary metabolites[J]. Journal of China Pharmaceutical University, 2018,49(2):129-135.
[18]	武临专, 洪斌. 微生物药物合成生物学研究进展[J]. 药学学报, 2013,48(2):155-160. pmid: 23672010
	Wu LZ, Hong B. Synthetic biology toward microbial secondary metabolites and pharmaceuticals[J]. Acta Pharmaceutica Sinica, 2013,48(2):155-160. URL pmid: 23672010
[19]	Komatsu M, Uchiyama T, Omura S, et al. Genome-minimized Streptomyces host for the heterologous express-ion of secondary metabolism[J]. Proc Natl Acad Sci USA, 2010,107(6):2646-2651. doi: 10.1073/pnas.0914833107 URL pmid: 20133795
[20]	Yanai K, Murakami T, Bibb M . Amplification of the entire kanam ycin biosynthetic gene cluster during em pirical strain im provem ent of Streptomyces kanamyceticus[J]. Proceedings of the National Academy of Sciences, 2006,103(25):9661-9666.
[21]	雷秀清, 李力, 黄建忠. 提高放线菌次级代谢产物产量方法的研究进展[J]. 生物技术通报, 2014(5):45-51.
	Lei XQ, Li L, Huang JZ. Research progress of improving the actinomycetes secondary metabolite production method[J]. Biotechnology Bulletin, 2014(5):45-51.
[22]	李晓梅, 林春燕, 逄爱萍, 等. 合成生物学在链霉菌次级代谢产物研发中的应用[J]. 中国生物工程杂志, 2015,35(4):92-97.
	Li XM, Lin CY, Pang AP, et al. Application of synthetic biology in research and development of the secondary metabolites from Streptomyces[J]. China Biotechnology, 2015,35(4):92-97.
[23]	Ochi K. From microbial differentiation to ribosome engineering[J]. Biosci Biotechnol Biochem, 2007,71(6):1373-1386. URL pmid: 17587668
[24]	Ochi K, Okamoto S, Tozawa Y, et al. Ribosome engineering and secondary metabolite production[J]. Advances in Applied Microbiology, 2004,56:155-184. doi: 10.1016/S0065-2164(04)56005-7 URL pmid: 15566979
[25]	杨康敏, 高向东, 顾觉奋. 激活沉默基因簇发掘微生物次级代谢产物的研究进展[J]. 中国医药生物技术, 2015,15(1):77-80.
	Yang KM, Gao XD, Gu JF. Research progress on the activation of silencing gene clusters to discover secondary metabolites of microorganisms[J]. Chin Med Biotechnol, 2015,15(1):77-80.
[26]	刘华华, 陈宇航, 陈敏. 核糖体工程技术选育阿维拉霉素高产菌株[J]. 农业生物技术学报, 2019,27(7):1322-1330.
	Liu HH, Chen YH, Chen M. Breeding of high avilamycin-producing strains by ribosome engineering[J]. Journal of Agricultural Biotechnology, 2019,27(7):1322-1330.
[27]	Gerke J, Bayram O, Feussner K, et al. Breaking the silence:protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans[J]. Appl Environ Microbiol. 2012,78(23):8234-8244. doi: 10.1128/AEM.01808-12 URL pmid: 23001671
[28]	盛楠, 顾觉奋. 激活沉默基因的方法及在微生物制药领域的新进展[J]. 中国新药杂志, 2014,23(18):2165-2168, 2184.
	Sheng N, Gu JF. Silent genes provide new ideas for microbial pharmaceutical research[J]. Chinese Journal of New Drugs, 2014,23(18):2165-2168, 2184.
[29]	Romero-Rodríguez A, Robledo-Casados I, Sánchez S. An overview on transcriptional regulators in Streptomyces[J]. BBA - Gene Regulatory Mechanisms, 2015,1849:1017-1039. doi: 10.1016/j.bbagrm.2015.06.007 URL pmid: 26093238
[30]	崔小清, 丁壮, 武莉, 等. 生合成途径特异性转录因子及其激活真菌沉默次级代谢产物的研究进展[J]. 中国海洋药物, 2017,36(4):75-82.
	Cui XQ, Ding Z, Wu L, et al. Research progress on the pathway-specific transcription factors and their application in activating cryptic fungal secondary metabolites[J]. Chinese Journal of Marine Drugs, 2017,36(4):75-82.
[31]	Angelo P, Birgit F, Gerald B, et al. A class 1 histone deacetylase as major regulator of secondary metabolite production in Aspergillus nidulans[J]. Frontiers in Microbiology, 2018,9:2212. doi: 10.3389/fmicb.2018.02212 URL pmid: 30283426
[32]	赵琪, 闵涛玲, 胡海峰. 激活微生物沉默基因簇合成新型天然产物的研究[J]. 世界临床药物, 2014,35(8):501-505.
	Zhao Q, Min TL, Hu HF. Studies on activating silent biosynthetic gene clusters to synthesize new natural products in microorganisms[J]. World Clinical Drugs, 2014,35(8):501-505.
[33]	Williams RB, Henrikson JC, Hoover AR, et al. Epigenetic remodeling of the fungal secondary metabolome[J]. Organic & Biomolecular Chemistry, 2008,6(11):1895-1897. doi: 10.1039/b804701d URL pmid: 18480899
[34]	Henrikson JC, Hoover AR, Joynera PM, Cichewicz RH. A chemical epigenetics approach for engineering the in situ biosynjournal of a cryptic natural product from Aspergillus niger[J]. Organic & Biomolecular Chemistry, 2009,7(3):435-438. doi: 10.1039/b819208a URL pmid: 19156306
[35]	Fisch KM, Gillaspy AF, Gipson M, et al. Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger[J]. J Ind Microbiol Biotechnol. 2009,36:1199-1213. doi: 10.1007/s10295-009-0601-4 URL pmid: 19521728
[36]	Wang WS, Li SS, Li ZL, et al. Harnessing the intracellular triacylglycerols for titer improvement of polyketides in Streptomyces[J]. Nature Biotechnology, 2020,38:76-83. doi: 10.1038/s41587-019-0335-4 URL pmid: 31819261
[37]	Fernandez-Martınez LT, Hoskisson PA. Expanding, integrating, sensing and responding:the role of primary metabolism in specialised metabolite production[J]. Microbiology, 2019,51:16-21.
[38]	Pan R, Bai XL, Chen JW. Exploring structural diversity of microbe secondary metabolites using OSMAC strategy:a literature review[J]. Frontiers in Microbiology, 2019,10. doi: 10.3389/fmicb.2019.03111 URL pmid: 32082268
[39]	Seyedsayamdost MR. High-through put platform for the discovery of elicitors of silent bacterial gene clusters[J]. Proc Natl Acad Sci USA, 2014,111(20):7266-7271. doi: 10.1073/pnas.1400019111 URL pmid: 24808135
[40]	Yan Q, Philmus B, Chang JH, et al. Novel mechanism of metabolic co-regulation coordinates the biosynjournal of secondary metabolites in Pseudomonas protegens[J]. eLife, 2017,6:e22835. doi: 10.7554/eLife.22835 URL pmid: 28262092