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Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.9 P.767-773


Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628

Author(s):  Yefeng HU, Juan WANG, Jie XU, Zheng MA, Andreas BECHTHOLD, Xiaoping YU

Affiliation(s):  Zhejiang Provincial Key Laboratory of Biometrology and Inspection & Quarantine, College of Life Sciences, China Jiliang University, Hangzhou 310018, China; more

Corresponding email(s):   mazheng520@163.com

Key Words:  S. diastatochromogenes 1628, SAM, MetK, Toyocamycin, Tetraene macrolides

Yefeng HU, Juan WANG, Jie XU, Zheng MA, Andreas BECHTHOLD, Xiaoping YU. Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628[J]. Journal of Zhejiang University Science B, 2021, 22(9): 767-773.

@article{title="Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628",
author="Yefeng HU, Juan WANG, Jie XU, Zheng MA, Andreas BECHTHOLD, Xiaoping YU",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628
%A Yefeng HU
%A Juan WANG
%A Jie XU
%A Zheng MA
%A Xiaoping YU
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 9
%P 767-773
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100115

T1 - Effects of S-adenosylmethionine on production of secondary metabolites in Streptomyces diastatochromogenes 1628
A1 - Yefeng HU
A1 - Juan WANG
A1 - Jie XU
A1 - Zheng MA
A1 - Andreas BECHTHOLD
A1 - Xiaoping YU
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 9
SP - 767
EP - 773
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100115

Streptomyces are famous for their ability to synthesize a large number of bioactive compounds as secondary metabolites containing antibiotics, enzyme inhibitors, and other small molecules with potential physiological activity (Niu et al., 2016; Song et al., 2019; Yin et al., 2019). Secondary metabolites are produced by a multi-step reaction of a primary metabolite as a precursor (Liu et al., 2013; Li et al., 2021). Therefore, it is of great research significance to increase the overall synthesis level of antibiotics by increasing the amount of synthesis of precursors.


目的:考察S-腺苷甲硫氨酸(SAM)对淀粉酶产色链霉菌(Streptomyces diastatochromogenes)1628次级代谢产物产量的影响。
创新点:SAM是甲基的重要供体,可为次级代谢产物提供前体,同时也可以作为信号增强次级代谢产物合成基因的表达。因此,本研究首次探究了SAM与S. diastatochromogenes1628次级代谢产物合成的相关性。
方法:S. diastatochromogenes1628为对象,通过体外添加SAM以及在S. diastatochromogenes1628体内过表达、敲除和回补SAM编码基因metKsd,考察S. diastatochromogenes1628次级代谢产物产量的变化。
结论:由于渗透性差,外源添加SAM对S. diastatochromogenes1628合成次级代谢产物(丰加霉素和三种四烯大环内酯类抗生素:四霉素A、四霉素P和四烯菌素B)没有影响;敲除、回补和过表达基因metKsd证实增加胞内SAM可提高S. diastatochromogenes1628三种四烯大环内酯类抗生素的产量,且可促进四烯大环内酯类化合物合成关键基因的表达,而胞内SAM浓度的变化对丰加霉素的产量和及其关键基因的表达均无明显影响。


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[1]BattagliaU, LongJE, SearleMS, et al., 2011. 7-Deazapurine biosynthesis: NMR study of toyocamycin biosynthesis in Streptomyces rimosus using 2-13C-7-15N-adenine. Org Biomol Chem, 9(7):2227-2232.

[2]CaoB, YaoF, ZhengXQ, et al., 2012. Genome mining of the biosynthetic gene cluster of the polyene macrolide antibiotic tetramycin and characterization of a P450 monooxygenase involved in the hydroxylation of the tetramycin B polyol segment. ChemBioChem, 13(15):2234-2242.

[3]CuiH, NiXP, ShaoW, et al., 2015. Functional manipulations of the tetramycin positive regulatory gene ttmRIV to enhance the production of tetramycin A and nystatin A1 in Streptomyces ahygroscopicus. J Ind Microbiol Biotechnol, 42(9):1273-1282.

[4]CuiH, NiXP, LiuSJ, et al., 2016. Characterization of three positive regulators for tetramycin biosynthesis in Streptomyces ahygroscopicus. FEMS Microbiol Lett, 363(12):fnw109.

[5]FanJX, SongY, TangG, et al., 2020. Substantial improvement of tetraene macrolide production in Streptomyces diastatochromogenes by cumulative drug resistance mutations. PLoS ONE, 15(5):e0232927.

[6]GuYY, WangXM, ChaoY, et al., 2016. Effects of chromosomal integration of the Vitreoscilla hemoglobin gene (vgb) and S-adenosylmethionine synthetase gene (metK) on ε‍-poly-L-lysine synthesis in Streptomyces albulus NK660. Appl Biochem Biotechnol, 178(7):1445-1457.

[7]HuhJH, KimDJ, ZhaoXQ, et al., 2004. Corrigendum to “Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in streptomycetes” [FEMS Microbiol Lett. 238 (2004) 439-447]. FEMS Microbiol Lett, 238(2):245.

[8]KimDJ, HuhJH, YangYY, et al., 2003. Accumulation of S-adenosyl-L-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23. J Bacteriol, 185(2):592-600.

[9]LiSS, LiZL, PangS, et al., 2021. Coordinating precursor supply for pharmaceutical polyketide production in Streptomyces. Curr Opin Biotechnol, 69:26-34.

[10]LiaoZJ, SongZQ, XuJ, et al., 2020. Identification of a gene from Streptomyces rimosus M527 negatively affecting rimocidin biosynthesis and morphological differentiation. Appl Microbiol Biotechnol, 104(23):10191-10202.

[11]LiuG, ChaterKF, ChandraG, et al., 2013. Molecular regulation of antibiotic biosynthesis in Streptomyces. Microbiol Mol Biol Rev, 77(1):112-143.

[12]LiuQ, LinQ, LiXY, et al., 2020. Construction and application of a “superplasmid” for enhanced production of antibiotics. Appl Microbiol Biotechnol, 104(4):1647-1660.

[13]MaZ, LiuJX, BechtholdA, et al., 2014a. Development of intergeneric conjugal gene transfer system in Streptomyces diastatochromogenes 1628 and its application for improvement of toyocamycin production. Curr Microbiol, 68(2):180-185.

[14]MaZ, TaoLB, BechtholdA, et al., 2014b. Overexpression of ribosome recycling factor is responsible for improvement of nucleotide antibiotic-toyocamycin in Streptomyces diastatochromogenes 1628. Appl Microbiol Biotechnol, 98(11):5051-5058.

[15]MaZ, LuoS, XuXH, et al., 2016. Characterization of representative rpoB gene mutations leading to a significant change in toyocamycin production of Streptomyces diastatochromogenes 1628. J Ind Microbiol Biotechnol, 43(4):463-471.

[16]MaZ, HuYF, LiaoZJ, et al., 2020. Cloning and overexpression of the toy cluster for titer improvement of toyocamycin in Streptomyces diastatochromogenes. Front Microbiol, 11:2074.

[17]MaharjanS, OhTJ, LeeHC, et al., 2008. Heterologous expression of metK1-sp and afsR-sp in Streptomyces venezuelae for the production of pikromycin. Biotechnol Lett, 30(9):1621-1626.

[18]McCartyRM, BandarianV, 2008. Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin. Chem Biol, 15(8):790-798.

[19]NiuGQ, ChaterKF, TianYQ, et al., 2016. Specialised metabolites regulating antibiotic biosynthesis in Streptomyces spp. FEMS Microbiol Rev, 40(4):554-573.

[20]OhTJ, NiraulaNP, LiouK, et al., 2010. Identification of the duplicated genes for S-adenosyl-L-methionine synthetase (metK1-sp and metK2-sp) in Streptomyces peucetius var. caesius ATCC 27952. J Appl Microbiol, 109(2):398-407.

[21]OkamotoS, LezhavaA, HosakaT, et al., 2003. Enhanced expression of S-adenosylmethionine synthetase causes overproduction of actinorhodin in Streptomyces coelicolor A3(2). J Bacteriol, 185(2):601-609.

[22]ParkHS, ShinSK, YangYY, et al., 2005. Accumulation of S-adenosylmethionine induced oligopeptide transporters including BldK to regulate differentiation events in Streptomyces coelicolor M145. FEMS Microbiol Lett, 249(2):199-206.

[23]RenJ, CuiYQ, ZhangF, et al., 2014. Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus. Microbiol Res, 169(7-8):602-608.

[24]ShengY, OuYX, HuXJ, et al., 2020. Generation of tetramycin B derivative with improved pharmacological property based on pathway engineering. Appl Microbiol Biotechnol, 104(6):2561-2573.

[25]ShentuX, LiDT, XuJF, et al., 2016. Effects of fungicides on the yeast-like symbiotes and their host, Nilaparvata lugens Stål (Hemiptera: Delphacidae). Pestic Biochem Physiol, 128:16-21.

[26]SongZQ, LiaoZJ, HuYF, et al., 2019. Development and optimization of an intergeneric conjugation system and analysis of promoter activity in Streptomyces rimosus M527. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(11):891-900.

[27]SongZQ, MaZ, BechtholdA, et al., 2020. Effects of addition of elicitors on rimocidin biosynthesis in Streptomyces rimosus M527. Appl Microbiol Biotechnol, 104(10):4445-4455.

[28]TianPP, CaoP, HuD, et al., 2017. Comparative metabolomics reveals the mechanism of avermectin production enhancement by S-adenosylmethionine. J Ind Microbiol Biotechnol, 44(4-5):595-604.

[29]WangT, BaiLQ, ZhuDQ, et al., 2012. Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes. Enzyme Microb Technol, 50(1):5-9.

[30]WangY, BoghigianBA, PfeiferBA, 2007. Improving heterologous polyketide production in Escherichia coli by overexpression of an S-adenosylmethionine synthetase gene. Appl Microbiol Biotechnol, 77(2):367-373.

[31]XuJ, SongZQ, XuXH, et al., 2019. ToyA, a positive pathway-specific regulator for toyocamycin biosynthesis in Streptomyces diastatochromogenes 1628. Appl Microbiol Biotechnol, 103(17):7071-7084.

[32]XuYR, TanGQ, KeML, et al., 2018. Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis. J Ind Microbiol Biotechnol, 45(5):345-355.

[33]YinHZ, WangWS, FanKQ, et al., 2019. Regulatory perspective of antibiotic biosynthesis in Streptomyces. Sci China Life Sci, 62(5):698-700.

[34]ZhangXC, FenMQ, ShiXL, et al., 2008. Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces actuosus leads to increased production of nosiheptide. Appl Microbiol Biotechnol, 78(6):991-995.

[35]ZhaoXH, ZhongLJ, ZhangQH, et al., 2010. Effect of tetramycin on mycelial growth and spore germination of rice blast pathogen. J Microbiol, 30(2):43-45 (in Chinese).

[36]ZhaoXQ, GustB, HeideL, 2010. S-adenosylmethionine (SAM) and antibiotic biosynthesis: effect of external addition of SAM and of overexpression of SAM biosynthesis genes on novobiocin production in Streptomyces. Arch Microbiol, 192(4):289-297.

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