• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

代谢调控技术在放线菌生物合成抗生素的应用进展

张亚, 周长林

张亚, 周长林. 代谢调控技术在放线菌生物合成抗生素的应用进展[J]. 中国药科大学学报, 2015, 46(4): 393-399. DOI: 10.11665/j.issn.1000-5048.20150402
引用本文: 张亚, 周长林. 代谢调控技术在放线菌生物合成抗生素的应用进展[J]. 中国药科大学学报, 2015, 46(4): 393-399. DOI: 10.11665/j.issn.1000-5048.20150402
ZHANG Ya, ZHOU Changlin. Application of metabolic regulation in the antibiotic biosynthesis of actinomycetes[J]. Journal of China Pharmaceutical University, 2015, 46(4): 393-399. DOI: 10.11665/j.issn.1000-5048.20150402
Citation: ZHANG Ya, ZHOU Changlin. Application of metabolic regulation in the antibiotic biosynthesis of actinomycetes[J]. Journal of China Pharmaceutical University, 2015, 46(4): 393-399. DOI: 10.11665/j.issn.1000-5048.20150402

代谢调控技术在放线菌生物合成抗生素的应用进展

基金项目: 中央高校基本科研业务费专项资金资助项目(No.ZL2014SK0035);江苏高校优势学科建设工程资助项目

Application of metabolic regulation in the antibiotic biosynthesis of actinomycetes

  • 摘要: 放线菌的次级代谢产物丰富多样,一直是抗生素及其先导化合物的主要来源之一。通过遗传操作来改造放线菌,代谢调控其抗生素的生物合成也是近年来微生物次级代谢的研究热点。结合近年来的研究成果,从调节调控基因表达,增加基因簇拷贝数及基因簇的异源表达,过表达抗性基因和转运基因,提高前体代谢通量和核糖体工程等方面综述了代谢调控技术在放线菌生物合成抗生素的应用进展。
    Abstract: The secondary metabolites of actinomycetes are rich and diverse, which have become important sources of antibiotics and their lead compounds. The study of microbial secondary metabolism is focused on metabolic regulation of antibiotic biosynthesis in actinomycetes by genetic manipulation. On the basis of the advances of recent years, this paper summarizes the application progress of metabolic regulation used for improving biosynthesis of antibiotics in actinomycetes, concluding of regulating the expression of regulatory genes, increasing the copy numbers of gene clusters and heterologous expression, over-expressing the resistance genes and transfer gene, improving precursor metabolic flux, and ribosome engineering.
  • [1] Bérdy J. Thoughts and facts about antibiotics:where we are now and where we are heading[J].J Antibiot,2012, 65(8):385-395.
    [2] Olano C,Lombó F,Méndez C,et al.Improving production of bioactive secondary metabolites in actinomycetes by metabolic engineering[J].Metab Eng,2008, 10(5):281-292.
    [3] Rey DA,Nentwich SS,Koch DJ,et al.The McbR repressor modulated by the effector substance S-adenosylhomocysteine controls directly the transcription of a regulon involved in sulphur metabolism of Corynebacterium glutamicum ATCC 13032[J].Mol Microbiol,2005, 56(4):871-887.
    [4] Orth P,Schnappinger D,Hillen W,et al.Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system[J].Nat Struct Biol,2000, 7(3):215-219.
    [5] Zhu Q,Li J,Ma J,et al.Discovery and engineered overproduction of antimicrobial nucleoside antibiotic A201A from the deep-sea marine actinomycete Marinactinospora thermotolerans SCSIO 00652[J].Antimicrob Agents Chemother,2012, 56(1):110-114.
    [6] Zhang Y,Zou Z,Niu G,et al.JadR and jadR2 act synergistically to repress jadomycin biosynthesis[J].Sci China Life Sci,2013, 56(7):584-590.
    [7] Dun J, Zhao Y, Zheng G, et al. PapR6, a putative atypical response regulator,functions as a pathway-specific activator of pristinamycin II biosynthesis in Streptomyces pristinaespiralis[J].J Bacteriol,2015, 197(3):441-450.
    [8] Alvarez-álvarez R,Rodríguez-García A,Santamarta I,et al.Transcriptomic analysis of Streptomyces clavuligerus ΔccaR::tsr:effects of the cephamycin C-clavulanic acid cluster regulator CcaR on global regulation[J].Microb Biotechnol,2014, 7(3):221-231.
    [9] Flórez AB,Alvarez S,Zabala D,et al.Transcriptional regulation of mithramycin biosynthesis in Streptomyces argillaceus:dual role as activator and repressor of the PadR-like regulator MtrY[J].Microbiology,2014, 161(Pt 2):272-284.
    [10] Kurniawan YN,Kitani S,Maeda A,et al.Differential contributions of two SARP family regulatory genes to indigoidine biosynthesis in Streptomyces lavendulae FRI-5[J].Appl Microbiol Biotechnol,2014, 98(23):9713-9721.
    [11] Novakova R,Rehakova A,Kutas P,et al.The role of two SARP family transcriptional regulators in regulation of the auricin gene cluster in Streptomyces aureofaciens CCM 3239[J].Microbiology,2011, 157(Pt 6):1629-1639.
    [12] Rehakova A,Novakova R,Feckova L,et al.A gene determining a new member of the SARP family contributes to transcription of genes for the synthesis of the angucycline polyketide auricin in Streptomyces aureofaciens CCM 3239[J].FEMS Microbiol Lett,2013, 346(1):45-55.
    [13] Xie Y,Wang B,Liu J,et al.Identification of the biosynthetic gene cluster and regulatory cascade for the synergistic antibacterial antibiotics griseoviridin and viridogrisein in Streptomyces griseoviridis[J].Chembiochem,2012, 13(18):2745-2757.
    [14] Nah JH,Park SH,Yoon HM,et al.Identification and characterization of wblA-dependent tmcT regulation during tautomycetin biosynthesis in Streptomyces sp.CK4412[J].Biotechnol Adv,2012, 30(1):202-209.
    [15] Gao C,Hindra,Mulder D,et al.Crp is a global regulator of antibiotic production in streptomyces[J].MBio,2012, 3(6).pii:e00407-12.doi: 10.1128/mBio.00407-12.
    [16] MeKenzie NL,Thaker M,Koteva K,et al.Induction of antimicrobial activities in heterologous streptomycetes using alleles of the Streptomyces coelicolor gene absA1[J].J Antibiot,2010, 63(4):177-182.
    [17] Yepes A,Rico S,Rodríguez-García A,et al.Novel two-component systems implied in antibiotic production in Streptomyces coelicolor[J].PLoS One,2011, 6(5):1371-1381.
    [18] Makitrynskyy R,Rebets Y,Ostash B,et al.Genetic factors that influence moenomycin production in Streptomyces[J].J Ind Microbiol Biotechnol,2010, 37(6):559-566.
    [19] Jiang LB,Liu YP,Wang P,et al.Inactivation of the extracytoplasmic function sigma factor Sig6 stimulates avermectin production in Streptomyces avermitilis[J].Biotechnol Lett,2011, 33(10):1955-1961.
    [20] Kang SH,Huang J,Lee HN,et al.Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces[J].J Bacteriol,2007, 189(11):4315-4319.
    [21] Fowler-Goldsworthy K,Gust B,Mouz S,et al.The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2)[J].Microbiology,2011, 157(Pt 5):1312-1328.
    [22] Rabyk M, Ostash B, Rebets Y, et al. Streptomyces ghanaensis pleiotropic regulatory gene wblAgh influences morphogenesis and moenomycin production[J].Biotechnol Lett,2011, 33(12):2481-2486.
    [23] Noh JH,Kim SH,Lee HN,et al.Isolation and genetic manipulation of the antibiotic down-regulatory gene,wblA ortholog for doxorubicin-producing Streptomyces strain improvement[J].Appl Microbiol Biotechnol,2010, 86(4):1145-1153.
    [24] 'Switek MA,Gubbens J,Bucca G,et al.The ROK family regulator Rok7B7 pleiotropically affects xylose utilization,carbon catabolite repression,and antibiotic production in Streptomyces coelicolor[J].J Bacteriol,2013, 195(6):1236-1248.
    [25] Wang T,Bai L,Zhu D,et al.Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes[J].Enzyme Microb Technol,2012, 50(1):5-9.
    [26] Pan Y,Wang L,He X,et al.SabR enhances nikkomycin production via regulating the transcriptional level of sanG,a pathway-specific regulatory gene in Streptomyces ansochromogenes[J].BMC Microbiol,2011, 11:164.
    [27] Zhou TC,Kim BG,Zhong JJ. Enhanced production of validamycin A in Streptomyces hygroscopicus 5008 by engineering validamycin biosynthetic gene cluster[J].Appl Microbiol Biotechnol,2014, 98(18):7911-7922.
    [28] Liao G,Li J,Li L,et al.Cloning,reassembling and integration of the entire nikkomycin biosynthetic gene cluster into Streptomyces ansochromogenes lead to an improved nikkomycin production[J].Microb Cell Fact,2010, 9:6.
    [29] Liao G,Wang L,Liu Q,et al.Manipulation of kynurenine pathway for enhanced daptomycin production in Streptomyces roseosporus[J].Biotechnol Prog,2013, 29(4):847-852.
    [30] Bachmann BO,Van Lanen SG,Baltz RH.Microbial genome mining for accelerated natural products discovery:is a renaissance in the making[J]?J Ind Microbiol Biotechnol,2014, 41(2):175-184.
    [31] Luo Y,Huang H,Liang J,et al.Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster[J].Nat Commun,2013, 4:2894.
    [32] Komatsu M,Komatsu K,Koiwai H,et al.Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites[J].ACS Synth Biol,2013, 2(7):384-396.
    [33] Jin Z,Jin X,Jin Q,et al.Conjugal transferring of resistance gene PTR for improvement of pristinamycin-producing Streptomyces pristinaespiralis[J].Appl Biochem Biotechnol,2010, 160(6):1853-1864.
    [34] Qiu J,Zhuo Y,Zhu D,et al.Overexpression of the ABC transporter AvtAB increases avermectin production in Streptomyces avermitilis[J].Appl Microbiol Biotechnol,2011, 92(2):337-345.
    [35] Yu L,Yan X,Wang L,et al.Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus[J].BMC Biotechnol,2012, 12:52.
    [36] Zabala D, Braña AF, AB Flórez, et al. Engineering precursor metabolite pools for increasing production of antitumor mithramycins in Streptomyces argillaceus[J].Metab Eng,2013,20:187-197.
    [37] Qin Z,Wang X,Rateb ME,et al.Disruption of a methyltransferase gene in actinomycin G gene cluster in Streptomyces iakyrus increases the production of phenazinomycin[J].FEMS Microbiol Lett,2014, 352(1):62-68.
    [38] Ren J,Cui Y,Zhang F,et al.Enhancement of nystatin production by redirecting precursor fluxes after disruption of the tetramycin gene from Streptomyces ahygroscopicus[J].Microbiol Res,2014, 169(7/8):602-608.
    [39] Ma Z,Tao L,Bechthold A,et al.Overexpression of ribosome recycling factor is responsible for improvement of nucleotide antibiotic-toyocamycin in Streptomyces diastatochromogenes 1628[J].Appl Microbiol Biotechnol,2014, 98(11):5051-5058.
    [40] Pan Y, Lu C, Dong H, et al. Disruption of rimP-SC, encoding a ribosome assembly cofactor,markedly enhances the production of several antibiotics in Streptomyces coelicolor[J].Microb Cell Fact,2013, 12:65.
计量
  • 文章访问数:  1118
  • HTML全文浏览量:  1
  • PDF下载量:  1893
  • 被引次数: 0
出版历程
  • 刊出日期:  2015-08-24

目录

    /

    返回文章
    返回
    x 关闭 永久关闭