科微学术

微生物学通报

林可霉素生物合成及其分子调控研究进展
作者:
基金项目:

合肥师范学院引进高层次人才科研启动基金(2020rcjj36);安徽省药食同源科研平台专项项目(2020PT20);安徽省高校自然科学基金(KJ2021A0918)


Biosynthesis and molecular regulation of lincomycin: a review
Author:
  • 摘要
  • | |
  • 访问统计
  • |
  • 参考文献 [66]
  • |
  • 相似文献
  • |
  • 引证文献
  • | |
  • 文章评论
    摘要:

    林可霉素(lincomycin)是由林可链霉菌(Streptomyces lincolnensis)产生的酰胺类抗生素,在临床上主要用于治疗革兰氏阳性菌引起的感染。鉴于其具有高药用价值和经济价值,林可霉素生物合成和分子调控备受关注,并取得了较好的研究进展。本文综述了林可霉素的特征结构和生物合成,并重点介绍了林可链霉菌中林可霉素的分子调控机制等方面的研究进展,有利于深入认识林可链霉菌次级代谢调控网络,为在林可霉素高产菌中改造调控因子或其靶点元件提高产量提供理论指导。

    Abstract:

    Lincomycin, an amide antibiotic produced by Streptomyces lincolnensis, is mainly used to treat infections caused by Gram-positive bacteria in clinical practice. In view of its high medicinal value and economic value, progress has been achieved in the biosynthesis and molecular regulation of lincomycin. This review introduces the structural features and biosynthesis of lincomycin, and summarizes the research progress in the molecular regulatory mechanism of lincomycin in S. lincolnensis. The review is conducive to the in-depth understanding of the secondary metabolic regulatory network of S. lincolnensis and provides theoretical guidance for the transformation of regulatory factors or their target elements in the strains with high yields of lincomycin.

    参考文献
    [1] DUNKLE JA, XIONG LQ, MANKIN AS, CATE JHD. Structures of the Escherichia coli ribosome with antibiotics bound near the peptidyl transferase center explain spectra of drug action[J]. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(40):17152-17157.
    [2] SPÍŽEK J, ŘEZANKA T. Lincomycin, clindamycin and their applications[J]. Applied Microbiology and Biotechnology, 2004, 64(4):455-464.
    [3] ZHAO QF, WANG M, XU DX, ZHANG QL, LIU W. Metabolic coupling of two small-molecule thiols programs the biosynthesis of lincomycin A[J]. Nature, 2015, 518(7537):115-119.
    [4] WANG M, ZHAO QF, ZHANG QL, LIU W. Differences in PLP-dependent cysteinyl processing lead to diverse S-functionalization of lincosamide antibiotics[J]. Journal of the American Chemical Society, 2016, 138(20):6348-6351.
    [5] KOBERSKA M, VESELA L, VIMBERG V, LENART J, VESELA J, KAMENIK Z, JANATA J, BALIKOVA NOVOTNA G. Beyond self-resistance:ABCF ATPase LmrC is a signal-transducing component of an antibiotic-driven signaling cascade accelerating the onset of lincomycin biosynthesis[J]. mBio, 2021, 12(5):e0173121.
    [6] LIN CY, PANG AP, ZHANG Y, QIAO JJ, ZHAO GR. Comparative transcriptomic analysis reveals the significant pleiotropic regulatory effects of LmbU on lincomycin biosynthesis[J]. Microbial Cell Factories, 2020, 19(1):1-16.
    [7] WANG RD, CAO Y, KONG FJ, HOU BB, ZHAO JQ, KANG YJ, YE J, WU HZ, ZHANG HZ. Developmental regulator RamRsl controls both morphological development and lincomycin biosynthesis in Streptomyces lincolnensis[J]. Journal of Applied Microbiology, 2022, 133(2):400-409.
    [8] XU YR, TANG YQ, WANG N, LIU J, CAI XL, CAI HY, LI J, TAN GQ, LIU RH, BAI LQ, ZHANG LX, WU H, ZHANG BC. Transcriptional regulation of a leucine-responsive regulatory protein for directly controlling lincomycin biosynthesis in Streptomyces lincolnensis[J]. Applied Microbiology and Biotechnology, 2020, 104(6):2575-2587.
    [9] XU YR, KE ML, LI J, TANG YQ, WANG N, TAN GQ, WANG YS, LIU RH, BAI LQ, ZHANG LX, WU H, ZHANG BC. TetR-type regulator SLCG_2919 is a negative regulator of lincomycin biosynthesis in Streptomyces lincolnensis[J]. Applied and Environmental Microbiology, 2019. DOI:https://doi.org/10.1128/AEM.02091-18.
    [10] XU YR, TAN GQ, KE ML, LI J, TANG YQ, MENG ST, NIU JJ, WANG YS, LIU RH, WU H, BAI LQ, ZHANG LX, ZHANG BC. Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis[J]. Journal of Industrial Microbiology & Biotechnology, 2018, 45(5):345-355.
    [11] 许玉荣, 许婉莲, 徐晶晶, 赵明, 高亮, 吴杭. rRNA甲基转移酶LmrB基因突变对林可霉素生物合成的影响[J]. 生物学杂志, 2023, 40(1):40-45. XU YR, XU WL, XU JJ, ZHAO M, GAO L, WU H. Impact of gene mutation of the rRNA methyltransferase LmrB on the lincomycin biosynthesis in Streptomyces lincolnensis[J]. Journal of Biology, 2023, 40(1):40-45(in Chinese).
    [12] PANG AP, DU L, LIN CY, QIAO J, ZHAO GR. Co-overexpression of lmbW and metK led to increased lincomycin A production and decreased byproduct lincomycin B content in an industrial strain of Streptomyces lincolnensis[J]. Journal of Applied Microbiology, 2015, 119(4):1064-1074.
    [13] PESCHKE U, SCHMIDT H, ZHANG HZ, PIEPERSBERG W. Molecular characterization of the lincomycin-production gene cluster of Streptomyces lincolnensis 78-11[J]. Molecular Microbiology, 1995, 16(6):1137-1156.
    [14] 刘瑞华. 林可霉素生物合成的研究进展[J]. 微生物学通报, 2018, 45(5):1138-1145. LIU RH. Proceedings of lincomycin biosynthesis[J]. Microbiology China, 2018, 45(5):1138-1145(in Chinese).
    [15] SASAKI E, LIN chia-i, LIN KY, LIU HW. Construction of the octose 8-phosphate intermediate in lincomycin A biosynthesis:characterization of the reactions catalyzed by LmbR and LmbN[J]. Journal of the American Chemical Society, 2012, 134(42):17432-17435.
    [16] BRAHME NM, GONZALEZ JE, MIZSAK S, ROLLS J, HESSLER E, HURLEY LH. Biosynthesis of the lincomycins. 2. Studies using stable isotopes on the biosynthesis of methylthiolincosaminide moiety of lincomycin A[J]. Journal of the American Chemical Society, 1984, 106(25):7878-7883.
    [17] LIN CA, SASAKI E, ZHONG AS, LIU HW. In vitro characterization of LmbK and LmbO:identification of GDP-d-erythro-α-d-gluco-octose as a key intermediate in lincomycin A biosynthesis[J]. Journal of the American Chemical Society, 2014, 136(3):906-909.
    [18] NOVOTNA J, OLSOVSKA J, NOVAK P, MOJZES P, CHALOUPKOVA R, KAMENIK Z, SPIZEK J, KUTEJOVA E, MARECKOVA M, TICHY P, DAMBORSKY J, JANATA J. Lincomycin biosynthesis involves a tyrosine hydroxylating heme protein of an unusual enzyme family[J]. PLoS One, 2013, 8(12):e79974.
    [19] NEUSSER D, SCHMIDT H, SPIZÈK J, NOVOTNÀ J, PESCHKE U, KASCHABECK S, TICHY P, PIEPERSBERG W. The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in the conversion of l-tyrosine to propylproline during the biosynthesis of the antibiotic lincomycin A[J]. Archives of Microbiology, 1998, 169(4):322-332.
    [20] NOVOTNÁ J, HONZÁTKO A, BEDNÁŘ P, KOPECKÝ J, JANATA J, SPÍŽEK J. l-3,4-dihydroxyphenyl alanine-extradiol cleavage is followed by intramolecular cyclization in lincomycin biosynthesis[J]. European Journal of Biochemistry, 2004, 271(18):3678-3683.
    [21] KADLČÍK S, KUČERA T, CHALUPSKÁ D, GAŽÁK R, KOBĚRSKÁ M, ULANOVÁ D, KOPECKÝ J, KUTEJOVÁ E, NAJMANOVÁ L, JANATA J. Adaptation of an l-proline adenylation domain to use 4-propyl-l-proline in the evolution of lincosamide biosynthesis[J]. PLoS One, 2013, 8(12):e84902.
    [22] JIRASKOVA P, GAZAK R, KAMENIK Z, STEININGEROVA L, NAJMANOVA L, KADLCIK S, NOVOTNA J, KUZMA M, JANATA J. New concept of the biosynthesis of 4-alkyl-l-proline precursors of lincomycin, hormaomycin, and pyrrolobenzodiazepines:could a γ-glutamyltransferase cleave the C-C bond?[J]. Frontiers in Microbiology, 2016, 7:276.
    [23] ULANOVA D, NOVOTNÁ J, SMUTNÁ Y, KAMENÍK Z, GAZÁK R, SULC M, SEDMERA P, KADLCÍK S, PLHÁCKOVÁ K, JANATA J. Mutasynthesis of lincomycin derivatives with activity against drug-resistant staphylococci[J]. Antimicrobial Agents and Chemotherapy, 2010, 54(2):927-930.
    [24] NAJMANOVÁ L, KUTEJOVÁ E, KADLEC J, POLAN M, OLŠOVSKÁ J, BENADA O, NOVOTNÁ J, KAMENÍK Z, HALADA P, BAUER J, JANATA J. Characterization of N-demethyllincosamide methyltransferases LmbJ and CcbJ[J]. ChemBioChem, 2013, 14(17):2259-2262.
    [25] KAMENIK Z, KADLCIK S, RADOJEVIC B, JIRASKOVA P, KUZMA M, GAZAK R, NAJMANOVA L, KOPECKY J, JANATA J. Deacetylation of mycothiol-derived ʻwaste productʼ triggers the last biosynthetic steps of lincosamide antibiotics[J]. Chemical Science, 2016, 7(1):430-435.
    [26] USHIMARU R, LIN chia-i, SASAKI E, LIU HW. Characterization of enzymes catalyzing transformations of cysteine S-conjugated intermediates in the lincosamide biosynthetic pathway[J]. ChemBioChem, 2016, 17(17):1606-1611.
    [27] van WEZEL GP, McDOWALL KJ. The regulation of the secondary metabolism of Streptomyces:new links and experimental advances[J]. Natural Product Reports, 2011, 28(7):1311-1333.
    [28] LIU G, CHATER KF, CHANDRA G, NIU GQ, TAN HR. Molecular regulation of antibiotic biosynthesis in streptomyces[J]. Microbiology and Molecular Biology Reviews:MMBR, 2013, 77(1):112-143.
    [29] HOU BB, LIN YW, WU HZ, GUO MJ, PETKOVIC H, TAO LY, ZHU XY, YE J, ZHANG HZ. The novel transcriptional regulator LmbU promotes lincomycin biosynthesis through regulating expression of its target genes in Streptomyces lincolnensis[J]. Journal of Bacteriology, 2018. DOI:https://doi.org/10.1128/jb.00447-17.
    [30] HOU BB, ZHU XY, KANG YJ, WANG RD, WU HZ, YE J, ZHANG HZ. LmbU, a cluster-situated regulator for lincomycin, consists of a DNA-binding domain, an auto-inhibitory domain, and forms homodimer[J]. Frontiers in Microbiology, 2019, 10:989.
    [31] McCORMICK JR, FLÄRDH K. Signals and regulators that govern Streptomyces development[J]. FEMS Microbiology Reviews, 2012, 36(1):206-231.
    [32] CHATER KF, CHANDRA G. The evolution of development in Streptomyces analysed by genome comparisons[J]. FEMS Microbiology Reviews, 2006, 30(5):651-672.
    [33] HOU BB, TAO LY, ZHU XY, WU W, GUO MJ, YE J, WU HZ, ZHANG HZ. Global regulator BldA regulates morphological differentiation and lincomycin production in Streptomyces lincolnensis[J]. Applied Microbiology and Biotechnology, 2018, 102(9):4101-4115.
    [34] LI J, WANG N, TANG YQ, CAI XL, XU YR, LIU RH, WU H, ZHANG BC. Developmental regulator BldD directly regulates lincomycin biosynthesis in Streptomyces lincolnensis[J]. Biochemical and Biophysical Research Communications, 2019, 518(3):548-553.
    [35] HUANG R, LIU HL, ZHAO WW, WANG SQ, WANG SF, CAI J, YANG C. AdpA, a developmental regulator, promotes ε-poly-l-lysine biosynthesis in Streptomyces albulus[J]. Microbial Cell Factories, 2022, 21(1):1-20.
    [36] LU T, WU XH, CAO Q, XIA YZ, XUN LY, LIU HW. Sulfane sulfur posttranslationally modifies the global regulator AdpA to influence actinorhodin production and morphological differentiation of Streptomyces coelicolor[J]. mBio, 2022. DOI:https://doi.org/10.1128/mbio.03862-21.
    [37] KANG YJ, WU W, ZHANG FX, CHEN L, WANG RD, YE J, WU HZ, ZHANG HZ. AdpAlin regulates lincomycin and melanin biosynthesis by modulating precursors flux in Streptomyces lincolnensis[J]. Journal of Basic Microbiology, 2023, 63(6):622-631.
    [38] LU T, WANG QD, CAO Q, XIA YZ, XUN LY, LIU HW. The pleiotropic regulator AdpA regulates the removal of excessive sulfane sulfur in Streptomyces coelicolor[J]. Antioxidants, 2023, 12(2):312.
    [39] OHNISHI Y, YAMAZAKI H, KATO JY, TOMONO A, HORINOUCHI S. AdpA, a central transcriptional regulator in the A-factor regulatory cascade that leads to morphological development and secondary metabolism inStreptomyces griseus[J]. Bioscience, Biotechnology, and Biochemistry, 2005, 69(3):431-439.
    [40] PAN YY, LIU G, YANG HH, TIAN YQ, TAN HR. The pleiotropic regulator AdpA-l directly controls the pathway-specific activator of nikkomycin biosynthesis inStreptomyces ansochromogenes[J]. Molecular Microbiology, 2009, 72(3):710-723.
    [41] KANG YJ, WANG YY, HOU BB, WANG RD, YE J, ZHU XY, WU HZ, ZHANG HZ. AdpAlin, a pleiotropic transcriptional regulator, is involved in the cascade regulation of lincomycin biosynthesis in Streptomyces lincolnensis[J]. Frontiers in Microbiology, 2019, 10:2428.
    [42] CUTHBERTSON L, NODWELL JR. The TetR family of regulators[J]. Microbiology and Molecular Biology Reviews:MMBR, 2013, 77(3):440-475.
    [43] 倪静姝, 汪焰胜, 吴杭, 张部昌. 放线菌中与抗生素合成相关TetR家族转录因子的研究进展[J]. 微生物学通报, 2019, 46(2):407-414. NI JS, WANG YS, WU H, ZHANG BC. Progress in TetR family transcriptional regulator related to antibiotic synthesis in actinomycetes[J]. Microbiology China, 2019, 46(2):407-414(in Chinese).
    [44] LIU J, WANG YX, HE HY, DONG SN, TANG LJ, YANG ED, WANG WY, ZHANG BC. The leucine-responsive regulatory protein SCAB_Lrp modulates thaxtomin biosynthesis, pathogenicity, and morphological development in Streptomyces scabies[J]. Molecular Plant Pathology, 2023, 24(2):167-178.
    [45] LU ZL, ZHANG XT, DAI JL, WANG YG, HE WQ. Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis[J]. Microbial Cell Factories, 2019, 18(1):1-12.
    [46] LIU J, LI J, DONG H, CHEN YF, WANG YS, WU H, LI CR, WEAVER DT, ZHANG LX, ZHANG BC. Characterization of an Lrp/AsnC family regulator SCO3361, controlling actinorhodin production and morphological development in Streptomyces coelicolor[J]. Applied Microbiology and Biotechnology, 2017, 101(14):5773-5783.
    [47] LIU J, LI L, WANG YX, LI BW, CAI XL, TANG LJ, DONG SN, YANG ED, WU H, ZHANG BC. Joint engineering of SACE_Lrp and its target MarR enhances the biosynthesis and export of erythromycin in Saccharopolyspora erythraea[J]. Applied Microbiology and Biotechnology, 2021, 105(7):2911-2924.
    [48] LIU J, CHEN YF, LI L, YANG ED, WANG YS, WU H, ZHANG LX, WANG WY, ZHANG BC. Characterization and engineering of the Lrp/AsnC family regulator SACE_5717 for erythromycin overproduction in Saccharopolyspora erythraea[J]. Journal of Industrial Microbiology and Biotechnology, 2019, 46(7):1013-1024.
    [49] LIU J, CHEN YF, WANG WW, REN M, WU PP, WANG YS, LI CR, ZHANG LX, WU H, WEAVER DT, ZHANG BC. Engineering of an Lrp family regulator SACE_Lrp improves erythromycin production in Saccharopolyspora erythraea[J]. Metabolic Engineering, 2017, 39:29-37.
    [50] XU YR, XU WL, YI J, LI BL, LIU M, ZHANG MF, ZHENG Y, LIU RH, WU H, ZHANG BC. Transcriptomics-guided investigation of the SLCG_Lrp regulon provides new insights into its role for lincomycin biosynthesis[J]. Fermentation, 2023, 9(4):396.
    [51] BREKASIS D, PAGET MSB. A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2)[J]. The EMBO Journal, 2003, 22(18):4856-4865.
    [52] PAGELS M, FUCHS S, PANÉ-FARRÉ J, KOHLER C, MENSCHNER L, HECKER M, McNAMARRA PJ, BAUER MC, von WACHENFELDT C, LIEBEKE M, LALK M, SANDER G, von EIFF C, PROCTOR RA, ENGELMANN S. Redox sensing by a Rex-family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus[J]. Molecular Microbiology, 2010, 76(5):1142-1161.
    [53] LIU XC, CHENG YQ, LYU MY, WEN Y, SONG Y, CHEN Z, LI JL. Redox-sensing regulator Rex regulates aerobic metabolism, morphological differentiation, and avermectin production in Streptomyces avermitilis[J]. Scientific Reports, 2017, 7:44567.
    [54] HOU BB, WANG RD, ZOU JY, ZHANG FX, WU HZ, YE J, ZHANG HZ. A putative redox-sensing regulator Rex regulates lincomycin biosynthesis in Streptomyces lincolnensis[J]. Journal of Basic Microbiology, 2021, 61(9):772-781.
    [55] PAOLO SS, HUANG JQ, COHEN SN, THOMPSON CJ. Rag genes:novel components of the RamR regulon that trigger morphological differentiation in Streptomyces coelicolor[J]. Molecular Microbiology, 2006, 61(5):1167-1186.
    [56] O'CONNOR TJ, NODWELL JR. Pivotal roles for the receiver domain in the mechanism of action of the response regulator RamR of Streptomyces coelicolor[J]. Journal of Molecular Biology, 2005, 351(5):1030-1047.
    [57] MENG ST, WU H, WANG L, ZHANG BC, BAI LQ. Enhancement of antibiotic productions by engineered nitrate utilization in actinomycetes[J]. Applied Microbiology and Biotechnology, 2017, 101(13):5341-5352.
    [58] ZHU YP, WANG J, SU WY, LU T, LI AY, PANG XH. Effects of dual deletion of glnR and mtrA on expression of nitrogen metabolism genes in Streptomyces venezuelae[J]. Microbial Biotechnology, 2022, 15(6):1795-1810.
    [59] SUN D, LIU C, ZHU JR, LIU WJ. Connecting metabolic pathways:Sigma factors in Streptomyces spp.[J]. Frontiers in Microbiology, 2017, 8:2546.
    [60] CHO YH, LEE EJ, AHN BE, ROE JH. SigB, an RNA polymerase sigma factor required for osmoprotection and proper differentiation of Streptomyces coelicolor[J]. Molecular Microbiology, 2008, 42(1):205-214.
    [61] LEE EJ, KAROONUTHAISIRI N, KIM HS, PARK JH, CHA CJ, KAO CM, ROE JH. A master regulator σBgoverns osmotic and oxidative response as well as differentiation via a network of sigma factors in Streptomyces coelicolor[J]. Molecular Microbiology, 2005, 57(5):1252-1264.
    [62] SUN D, WANG Q, CHEN Z, LI JL, WEN Y. An alternative σ factor, σ8, controls avermectin production and multiple stress responses in Streptomyces avermitilis[J]. Frontiers in Microbiology, 2017, 8:736.
    [63] TU BB, MAO Y, WANG RD, KANG YJ, YE J, ZHANG HZ, WU HZ. An alternative σ factor σLsl regulates lincomycin production in Streptomyces lincolnensis[J]. Journal of Basic Microbiology, 2023, 63(2):190-199.
    [64] RODRÍGUEZ H, RICO S, DÍAZ M, SANTAMARÍA RI. Two-component systems in Streptomyces:key regulators of antibiotic complex pathways[J]. Microbial Cell Factories, 2013, 12(1):1-10.
    [65] NI H, MOHSIN A, GUO MJ, CHU J, ZHUANG YP. Two-component system AfrQ1Q2 involved in oxytetracycline biosynthesis of Streptomyces rimosus M4018 in a medium-dependent manner[J]. Journal of Bioscience and Bioengineering, 2020, 129(2):140-145.
    [66] WANG RD, ZHOU TY, KONG FJ, HOU BB, YE J, WU HZ, ZHANG HZ. AflQ1-Q2 represses lincomycin biosynthesis via multiple cascades in Streptomyces lincolnensis[J]. Applied Microbiology and Biotechnology, 2023, 107(9):2933-2945.
    相似文献
    引证文献
    网友评论
    网友评论
    分享到微博
    发 布
引用本文

许玉荣,刘梦,王静茹,吴杭,张部昌. 林可霉素生物合成及其分子调控研究进展[J]. 微生物学通报, 2023, 50(11): 5097-5109

复制
相关视频

分享
文章指标
  • 点击次数:380
  • 下载次数: 808
  • HTML阅读次数: 715
  • 引用次数: 0
历史
  • 收稿日期:2023-04-17
  • 录用日期:2023-06-10
  • 在线发布日期: 2023-11-06
  • 出版日期: 2023-11-20
文章二维码