邓子新
微生物分子遗传学、抗生素药物代谢工程与化学生物学领域
个性化签名
- 姓名:邓子新
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学术头衔:
博士生导师, 国家杰出青年科学基金获得者, 中国科学院院士,
- 职称:-
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学科领域:
微生物学
- 研究兴趣:微生物分子遗传学、抗生素药物代谢工程与化学生物学领域
邓子新教授,多年来,在微生物分子遗传学、抗生素药物代谢工程与化学生物学领域开拓进取,已逐步成长为我国在该领域的代表人物。发展了一系列重要抗生素产生菌的体内外分子操作技术,分离鉴定了一大批生物活性和化学类别多样性的、构成我国首创和独特知识产权的抗生素基因簇, 同时阐明了多个复杂抗生素合成途径相关基因簇的结构、功能、表达及调控之机理,提出了多个被公认的生物合成模型,还利用一系列与抗生素生物合成、代谢调控有关的因子, 通过组合生物合成与化学生物学手段, 提高了多个重要抗生素的产量,并设计形成了一系列新抗衍生物。这些系统性进展先后发表在《Chemistry & Biology》、《Mol. Micro.》、《J. Bacteriol.》等化学生物学和微生物学领域一些权威刊物上, 构成了一系列抗生素基因簇或其药物衍生物的专利, 代表了我国在微生物学及相关交叉领域的一系列突破。1991年被评为国家级有突出贡献的中青年专家, 获国务院颁发的政府特殊津贴;1992年获霍英东基金会"青年教师奖';1993年获首届中国青年科学家提名奖;1994年获“国家杰出青年科学基金”、农业部科技进步一等奖和"中国青年科技奖"; 1996年入选人事部"百千万人才工程"第一、二层次; 1991、1994、1997年三次获得美国洛氏基金会"生物技术生涯奖";1997年获"瑞典国王奖"; 2000年获美国康乃尔大学首届Tang-Cornell 中国学者奖。
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750
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成果数
11
邓子新, XIUFEN ZHOU, , ZIXIN DENG, DAVID A. HOPWOOD, AND TOBIAS KIESER, *
JOURNAL OF BACrERIOLOGY, Apr. 1994, p. 2096-2099 Vol. 176, No.7,-0001,():
-1年11月30日
4)HAU3 is a temperate Streptomyces phage with cohesive ends and a broad host range that includes Streptomyces hygroscopicus 10-22, a producer of antifungal compounds, but it fails to grow on Streptomyces lividans 66. Two phasmid derivatives were constructed that function as X cosmid vectors in Escherichia coli and as phages in Streptomyces spp.
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邓子新, E.Takano, , †, ‡, M. Tao, F. Long, Maurenne J. Bibb, L. Wang, W. Li, M.J. buttner, Mervyn J. Bibb, Z. X. Deng, and K. F. Chater, *
Molecular Microbiology (2003) 50 (2), 475-486,-0001,():
-1年11月30日
Streptomycetes are mycelial bactria that produce sporulating aeraial hyphae on solid medai. Bald (bld) mutants fail to form aerial mycelium under at Least some conditions. Bld A encodes the only tRNA species able to read the leucine condon UUA efficeiently, implying the involvement of a TTA-containing gene in initiating aerial growth. One candidate for such a gene was bldH, because the bldH109 mutant of Streptomyces coelicolor resembles bldA mutants in some aspects. In the similar to the Streptomyces griseus A factor-regulated adpAg, was found to complement the blodh109 mutant paritally at both single and multiple copies. The sequence of adpAc form the bldH109 mutant revealed a frameshift. A constructed in frame deletion of adpAc conferred a bald colony phenotype, and the mutant behaved like bldAmutants and bldH109 in its pattern of extracellular signal exchange. Both adpAc and AdpAg contin a TTA codon. A TTA-free version of adpAc was engineered by replacing the TTA leucine condon with a cognate TTG leucine codon. The adpA (TTA-TTG) gene could partially restore aerial mycelium formation to a bldA mutant when it was followed in cis by the gene ornA, as in the natural chromosomal arrangement. This indicated that the UUA condon in adpAc mRNA is the principal target throuth which bldA influences morphological differention. It also implied that translational arrest at the UUA codon in adpAc mRNA caused a polar effect on the downstream ornA, and that the poor translation of both genes contributes extensively to the deficeiency of aerial mycelium formation in bldA mutants. Unlike the situation in S. griseus, adpAc transcrpion does not depend on the host's y-buyrolactone singatlling system, at least in liquid cultures. In addition, sigma factor BldN, which is the homologue of an S. griseus sigma factor AdsA that is absent form adpAg mutants of S. Griseus, Was present in the constructed adpAc, Null Mutant of S. Coelicolor.
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邓子新, Yuhui Sun, , Xiufen Zhou, Hui Dong, Guoquan Tu, Min Wang, Bofei Wang, and Zixing Deng, *
Chemistry & Biology, Vol. 10, 431-441, May, 2003,-0001,():
-1年11月30日
The PKS genes for biolsynthesis of the polyether nanchangmycin are organized to encode two sets of proteins (six and seven ORFs, respectivly), but are separated by independent ORFs that encode and eqimerase, epoxidase and epoxide hydrolase, and, notably, and independent ACP. One of the PKS modules lacks a corresponding ACP. We propose that the process of oxidavtive cvclization to form the polyether structrue occurs whten the polyketide chain is still andchored on the independent ACP berore release. 4-O-methyl-L-rhodinose biolsynthesis and its transglycosylation involve four puattive genes, and requlation of nanchang-mycin biosynthesis seems to involve activation as well as repression. In-frame deletion of a KR6 domain generated the anachangmycin aglycone with loss of 4-O -methyl-L-rhodinose and antibacterial activity, in agreement specific biolsynthetic steps.
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邓子新, Yuhui sun. Xiufen Zhou. Guoquan Tu. Zixin Deng
Arch Microbiol (2003) 180: 101-107,-0001,():
-1年11月30日
A cluster encoding genes for the biosyntheresis of meilingmycin, a mzcrolide antibiotic structurally similar to avermectin and milbemycin a 11, was identified among seven uncharactreized polyketide synthase gene clusters isolated from Streptomyces nanchangensis NS 3226 by hybirdization with PCR products using primers derived from the sequences of aevE, aveF and a thioesterase do main of the avermectin biosynthetcin production, confirming that the gene cluster encodes biosynthesis of this important anthelminthic antibiotic compound. A sequenced 8.6-kb fragment had aveC and aveE homologues (meiC and meiE) linked together, as in the avermectin gene cluster, but the arrangement of aveF (meiF) and the thioesterase homolgues differed. The rusults should pave the way to producing novel insecticidal compounds by generating hybrids between the two pathways.
Antibiotic biosynthetic genes., Macrlide antibioctic., Plolyketdie synthease., Avermectin., Gene replacerment in Sterepomyces
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邓子新, ZHOINGJUN QIN, KAIMAN PENG, XIUFEN ZHOU, , RONGFANG LIANG, QI ZHOU, HUAKUI CHEN, DAVID A. HOPWOOD, TOBIAS KIESER, * AND ZIXIN DENG
JOURNAL OF BACTERIOLOGY, Apr. 1994, p. 2090-2095 Vol. 176, No.7,-0001,():
-1年11月30日
Streptomyces hygroscopicus 10-22 could not be tranformed with any of the commonly used Streptomyces plasmid vectors and was resitant to plaque formation by the Streptomyces phages C31 and R4. Repeated selection reslulted in the isolation of derivatioves of S. hygroscpicus 10-22 that could accept DNA propagated in Streptomyces lividans 66. These new strains, which include three that still produce the original antibiotics, and be used as hosts for gene cloning. Insertion of nonreplicationg vectors by homolgous rctombination and transpositon of Tn 4560 were demonstrated in S. hygroscopcus 10-22
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【期刊论文】Isolation and Characterization of Micromonospora PhageφHAU8 and Development into a Phasmid
邓子新, Xiaohua Li, , Xiufen Zhou, and Zixin Deng, *
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, July 2004, p. 3893-3897 Vol. 70, No.7,-0001,():
-1年11月30日
φHAU8, a temperate Micromonospora phage, which is capable of infecting Micromonospora sp. strains 40027 and A-M-01, was isolated. The φHAU8 virion has a polyhedral head and a flexible tail and has a small genome (ca. 42.5kb) with double-stranded DNA and cohesive ends. φHAU8 was most stable at 4℃ in Difco nutrient broth within a pH range of 6 to 12. φHAU8 plaque formation on Micromonospora sp. strain 40027 was optimal with 32mM Ca2+ and 30mM Mg2[1]. A lysogen, LXH8, was isolated from turbid plaques, and a phasmid derivative that functions as a cosmid vector in Escherichia coli and as a phage in Micromonospora sp. Strain 40027 was constructed. Pulsed-field gel electrophoresis of AseI-digested total DNA showed that HAU8 DNA integrates into the 500-kb AseI fragment of Micromonospora sp. strain 40027.
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邓子新, Yuhui Sun, , Xiufen Zhou, Jun Liu, Guiming Zhang, Guoquan Tu, Tobias Kieser and Zixin Deng
,-0001,():
-1年11月30日
Several independent gene clusters containing varying lengths of type I polyketide synthase genes were isolated from 'Streptoyces nanchangensis' NS3226, a producer of nanchangmycin and melingmycin. The former is a polyether compound similar to dianemycin and the latter is a macrolide compound similar to milbemycin, which shares the same macrolide ring as avermectin but has different side groups. Clusters A-H spanned about 133, 132, 104, 174, 122, 54, 37 and 59kb, respectively. Two systems were developed for functional analysis of the gene clusters by gene disruption or replacement. (1) streptomyces phage C31 and its derived vectors can infect and lysogenize this strain. (2) pSET152, an Escherichia coli plasmid with C31 attP site, and pHZ1358, a Streptomyces-Escherichia coli into NS3226 by conjugation. pHZ1358 was shown to be generally useful for generating mutant strains by gene disruption and replacement in NS3226 as well as in several other Streptomyces strains. A region in cluster A (~133kb) seemed to be involved in nanchangmcin production because replacement of svveral DNA fragments in this region by an apramycin resistance gene [aac3(IV)] gave rise to nanchangmycin non-producing mutants.
antibiotic biosynthetic genes,, dianemycin,, avermectin,, polyketide synthease,, gene replacement in St reptomyces
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邓子新, Xiaohua Li, Xiufen Zhou, and Zixing Deng *
APPLEIED AND ENVIRONMENTAL MICROBIOLOGY, June 2003, p. 3144-3151 vol. 69, No.6,-0001,():
-1年11月30日
Vector systems allowing autonomous or stite-specific integrative gene cloning were development fom Micromonon-spora sp. Strain 40027, a producer of the antibiotic formicin A. The autonomous system depends on the discovery of a low-copy-number, self-transmissible covalently closed circular plasmid, pJTU112 (ca. 14.1db), which was shown to be present in the progenitor strain in both integrated and autonomous sates. The copy numbers of bothe wile-type pJTU112 and three derivatives in of it can be amplified at least sixfold by addition of streptomycin to the culture medium. The integravive system was developed by the used of a pBR322-derived Escherichia coli plasmid vector, pSET152, mediated by the attP site of the Streptomyces phage C32. Both vectors can be transferred of the dnd gene cluster originating from streptomyces lividans 1326 into Micromonospora sp. strain 40027 demonstrated the use of the two systems.
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邓子新, Xiuhua Pang, , Xiufen Zhou, Yuhui Sun, and Zixin Deng , *
JOURNAL OF BACTERIOLOGY, Apr. 2002, p. 1958-1965 Vol. 184, No.7,-0001,():
-1年11月30日
The chromposomal DNA of Streptomyces lrygroscopicus 10-22, a Derivativer of strain 5102-6, was digested with several restriction endonouleases and analyzed by pulsed-field gel electrophoresis (PFGE). Digestions with Asel gave 11 fragments with a total length of ca. 7.39Mb. The AseI sites were mapped by Southren hybridizations using pqrtially digested genome fragments and linking cosmids as probes. PFGE analysis of DNA with and without proteinase K treatment, together with the hybridization results, suggested a linear organization with terminal proteins and large terminal inverted repeats. Some deletion mutants had cirular chromosomes.
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【期刊论文】A linear plasmid temperature-sensitive for relication in streptomyces hygroscopicus 10-22
邓子新, Xiuhua Pang a, b, Yuhui Sun a, Jun Liu a, Xiufen Zhou a, Zixin Deng a, *
FEMS Microbiology Letters 208(2002)25-28,-0001,():
-1年11月30日
Streptomyces hygroscopicus 10-22 harbors a conjugative, autonomously replicating linear plasmid pHZ6 of ca. 70kb, which shows no obvious homology with chromosomal DNA and is temperature-sensitive for replication, being stable in the host at 28℃ but easily lost at 37℃. On a lawn of the wild-bype S. hygroscopicus 10-22 cured of pHZ6, PhZ6 elicit pocks. Temperature sensityivity seemed to be a unique property for pHZ6 among six linear plasmids tested, including the well-known linear plasmids SLP2 in Streptomyces lividans 1326 and SCP1 in Streptomyces coelicolor A3(2). The distinct identity of pHZ6 from previously identifeied pHZ1-pHZ5 was demonstrated by the profile of relevant plasmids in six well-defined strains originated from. S. hygroscopicus 10-22
Linear plasmid, Tempreature-sensitive, Streptomyces
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