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NeoI represents a group of transcriptional repressors regulating the biosynthesis of multiple aminoglycosides

Science China Life Sciences 2024年

作者： Yue Li Xiangxi Meng Dong Li Xiulei Xia Jihui Zhang Yihua Chen huarong tan State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences University of Chinese Academy of Sciences

In general, the initiation or closure of antibiotic biosynthesis is determined by regulatory proteins, but most of their mechanisms of action remain unknown. The 2-deoxystreptamine-containing aminoglycosides（2-DOS AGs） form a unique category among antibiotics. Genomic analysis revealed that a group of hypothetical regulatory genes represented by neoI are widely distributed in the biosynthetic gene clusters（BGCs） of natural products from Streptomyces species, including several 2-DOS AGs. Only limited knowledge is available for the roles of NeoItype regulators although neomycin and some of the related AGs have been developed as therapeutic drugs for decades. This study focuses on the functional determination of neoI and its homologues situated in the BGCs of six AGs. We found that the yield of neomycin in neoI disruption mutant（ΔneoI） increased by 50% compared to the wild-type（WT） strain(（420.6±44.1） mg L-1), while it was partially restored by the complementation of neoI, demonstrating that NeoI acted as a repressor in neomycin biosynthesis. Further electrophoretic mobility shift assays（EMSAs） and DNase I footprinting assays indicated that NeoI could specifically bind to the promoter region between neoE and neoI with conserved nucleotides（5'-CVHYMRCHDKAGYGGACR-3'）, as determined by site-directed mutagenesis. Interestingly, cross-bindings of the NeoI homologues from the six different BGCs to their corresponding DNA targets were manifested, and the five exogenous NeoI homologues could complement NeoI function of repressing neomycin biosynthesis. Our results suggested that NeoI-type regulators represent widespread and conservative regulatory characteristics in the biosynthesis of 2-DOS AGs, which would be significant for optimizing the biosynthetic pathways of valuable commercialized aminoglycoside antibiotics.

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Biosynthesis and combinatorial biosynthesis of antifungal nucleoside antibiotics

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Science China(Life Sciences) 2017年第9期60卷 939-947页

作者： Guoqing Niu Jiazhen Zheng huarong tan State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China Biotechnology Research Center Southwest University Chongqing 400716 China University of Chinese Academy of Sciences Beijing 100049 China

There is an urgent need for new antifungal agents to treat or combat fungal infection in humans and *** nucleoside antibiotics are an important family of natural products with distinctive structural *** their biosynthetic machinery is of great importance for the improvement of antibiotics *** importantly,it is a requisite for combinatorial biosynthesis to create hybrid nucleoside *** herein focus on findings on the natural and designed biosynthesis of this important family of nucleoside antibiotics.

关键词： nucleoside antibiotics biosynthesis combinatorial biosynthesis

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基于蒙特卡罗模拟的庐江县土壤汞健康风险评估

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环境化学 2024年第9期43卷 3103-3113页

作者：王飞方凤满谭华荣马康葛磊林跃胜安徽师范大学地理与旅游学院芜湖241003 江淮流域地表过程与区域响应安徽省重点实验室芜湖241003

汞(Hg)是我国优先控制的环境污染物之一.本文选择安徽省庐江县作为研究区域,采集202个土壤样品,分析研究土壤Hg的分布特征及其成因,并采用蒙特卡罗(Monte Carlo)方法评估土壤Hg对人群的概率健康风险.结果表明,研究区土壤Hg的平均含量(0.... 详细信息

汞(Hg)是我国优先控制的环境污染物之一.本文选择安徽省庐江县作为研究区域,采集202个土壤样品,分析研究土壤Hg的分布特征及其成因,并采用蒙特卡罗(Monte Carlo)方法评估土壤Hg对人群的概率健康风险.结果表明,研究区土壤Hg的平均含量(0.055 mg·kg^(-1))超出原巢湖地区当地土壤环境背景值(0.033 mg·kg^(-1)),与全国其他地区相比,仍处于较低水平.表层土壤Hg含量空间分布不均,呈现出东南高西北低的特点.在中部县城区和东南部的矿区,土壤Hg含量较高,高含量区在局部区域呈点状分布.概率健康风险表明,庐江县土壤Hg导致的非致癌风险在可接受的范围内(HI1.06×10^(-2)>6.96×10^(-3)>6.35×10^(-3)).土壤Hg蒸气摄入是普通人群暴露于Hg的主要途径.

关键词：土壤汞蒙特卡罗健康风险不确定性庐江县

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Biosynthesis and molecular regulation of secondary metabolites in microorganisms

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Science China(Life Sciences) 2017年第9期60卷 935-938页

作者： Yue Li huarong tan Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

Antibiotics are most important compounds in microbial secondary *** we know,streptomycetes are a particularly abundant source of antibiotics and related compounds,providing more than half of medically important antimicrobial and antitumor *** environmental and physiological conditions influence the onset and level of antibiotic *** of improper use and abuse of antibiotics as well as the horizontal transfer of antibiotic resistance genes between bacteria by conjugation,transduction or transformation, these have led to the appearance of antibiotic resistance and the loss of antibiotic native efficiency.

关键词：微生物分子调控次生代谢生物合成滥用抗生素次级代谢产物抗生素耐药性抗肿瘤药物

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Microbial quorum sensing signaling molecules and their roles in the biosynthesis of natural products

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中国科学:生命科学英文版 2023年第10期66卷 2429-2432页

作者： Jihui Zhang huarong tan State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China

Microorganisms act as a double-edged sword that can bring benefits and diseases to *** physiological and metabolic processes are under precise control of intricate regulatory networks,in which signaling systems are critical for cells coordinating or competing with each other to overcome unfavorable environmental conditions,including the prompt and acute responses to endogenous or exogenous stimuli.

关键词： prompt overcome precise

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Biosynthesis and regulation of secondary metabolites in microorganisms

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Science China(Life Sciences) 2013年第7期56卷 581-583页

作者： NIU GuoQing tan huarong State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences

Secondary metabolites are organic compounds with complex chemical structures and diverse physiological functions. Secondary metabolites include antibiotics, pigments, and other bioactive compounds. Many of these compounds have important agricultural and medical applications. Microorganisms, especially actinomycetes and filamentous fungi, are noted as a rich source of bioactive secondary metabolites. Typically, each species produces several antibiotics, with the profile being species-specific.

关键词：次生代谢产物微生物生物合成生物活性化合物有机化合物调控次级代谢产物生理功能

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Assembly and features of secondary metabolite biosynthetic gene clusters in Streptomyces ansochromogenes

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Science China(Life Sciences) 2013年第7期56卷 609-618页

作者： ZHONG XingYu TIAN YuQing NIU GuoQing tan huarong State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences University of Chinese Academy of Sciences

A draft genome sequence of Streptomyces ansochromogenes 7100 was generated using 454 sequencing technology. In combination with local BLAST searches and gap filling techniques, a comprehensive antiSMASH-based method was adopted to assemble the secondary metabolite biosynthetic gene clusters in the draft genome of S. ansochromogenes. A total of at least 35 putative gene clusters were identified and assembled. Transcriptional analysis showed that 20 of the 35 gene clusters were expressed in either or all of the three different media tested, whereas the other 15 gene clusters were silent in all three different media. This study provides a comprehensive method to identify and assemble secondary metabolite biosynthetic gene clusters in draft genomes of Streptomyces, and will significantly promote functional studies of these secondary metabolite biosynthetic gene clusters.

关键词： secondary metabolite gene cluster assemble features draft genome

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jadR* and jadR2 act synergistically to repress jadomycin biosynthesis

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Science China(Life Sciences) 2013年第7期56卷 584-590页

作者： ZHANG YanYan ZOU ZhengZhong NIU GuoQing tan huarong State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences University of Chinese Academy of Sciences

The biosynthesis of antibiotics is controlled by cascade regulation involving cluster-situated regulators (CSRs) and pleiotropic regulators. Three CSRs have been identified in the jadomycin biosynthetic gene cluster, including one OmpR-type activator (JadR1) and two TetR-like repressors (JadR* and JadR2). To examine their interactions in jadomycin biosynthesis, a series of mutants were generated and tested for jadomycin production. We noticed that jadomycin production in the jadR*-jadR2 double mutant was increased dramatically compared with either single mutant. Transcriptional analysis showed that jadR* and jadR2 act synergistically to repress jadomycin production by inhibiting the transcription of jadR1. Furthermore, jadR* and jadR2 reciprocally inhibit each other. The complex interactions among these three CSRs may provide clues for the activation of the jadomycin gene cluster, which would otherwise remain silent without stimulation from stress signals.

关键词： jadR^* jadR2 jadomycin biosynthesis cluster-situated regulators (CSRs)

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A widespread response of Gram-negative bacterial acyl-homoserine lactone receptors to Gram-positive Streptomyces γ-butyrolactone signaling molecules

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Science China(Life Sciences) 2021年第10期64卷 1575-1589页

作者： Xiang Liu Wenxi Wang Junyue Li Yue Li Jihui Zhang huarong tan State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China

Cell-cell communication is critical for bacterial survival in natural habitats,in which miscellaneous regulatory networks are ***,elucidating the interaction networks of a microbial community has been hindered by the population *** study reveals thatγ-butyrolactone(GBL)molecules from Streptomyces species,the major antibiotic producers,can directly bind to the acyl-homoserine lactone(AHL)receptor of Chromobacterium violaceum and influence violacein production controlled by the quorum sensing(QS)***,the widespread responses of more Gram-negative bacterial AHL receptors to Gram-positive Streptomyces signaling molecules are *** on the cross-talk between GBL and AHL signaling systems,combinatorial regulatory circuits(CRC)are designed and proved to be workable in Escherichia coli(***).It is significant that the QS systems of Gram-positive and Gram-negative bacteria can be bridged via native Streptomyces signaling *** findings pave a new path for unlocking the comprehensive cell-cell communications in microbial communities and facilitate the exploitation of innovative regulatory elements for synthetic biology.

关键词： signaling communication cross-talk Gram-positive bacteria Streptomyces γ-butyrolactone Gram-negative bacteria acyl-homoserine lactone synthetic biology combinatorial regulatory circuit

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菜子湖湿地不同类型土壤重金属的垂直分布特征及迁移规律

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环境化学 2024年第3期43卷 933-941页

作者：葛磊方凤满周浩姚有如谭华荣王飞林跃胜安徽师范大学地理与旅游学院芜湖241003 江淮流域地表过程与区域响应安徽省重点实验室芜湖241003

湿地是全球三大生态系统之一,而重金属污染已经成为桎梏湿地生态功能的重要环境问题.本文以菜子湖湿地草滩和泥滩两种不同类型0—100 cm垂直剖面土壤为研究对象,通过对比实验方法,分析菜子湖湿地土壤剖面8种重金属元素(As、Co、Cr、Cu... 详细信息

湿地是全球三大生态系统之一,而重金属污染已经成为桎梏湿地生态功能的重要环境问题.本文以菜子湖湿地草滩和泥滩两种不同类型0—100 cm垂直剖面土壤为研究对象,通过对比实验方法,分析菜子湖湿地土壤剖面8种重金属元素(As、Co、Cr、Cu、Ni、Pb、V、Zn)的垂向分布特征及迁移规律.结果表明,从整体剖面来看,除Cr、Cu和Pb外,其余重金属元素均不同程度超过安庆市土壤背景值,尤以表层土壤较为严重,说明当地存在重金属累积现象;根据土壤垂直分布来看,草滩和泥滩土壤重金属含量垂向变化较一致,总体表现出随土层深度的增加而逐渐减少的趋势,其中,草滩变化规律较为明显,而泥滩变化规律则稍显复杂;As、Co、Ni和V在草滩和泥滩整个剖面中的迁移系数均大于0,表明存在不同程度的富集,尤以As较为严重;Cu和Cr在两种类型土壤剖面中以富集为主,部分土层深度流失;Pb和Zn在垂直剖面土壤中的迁移特征较相似,均表现为在土壤表层富集,在中底层流失.研究结果可为沿江湿地环境保护提供理论支撑和科学依据.

关键词：湿地土壤重金属垂直分布迁移规律菜子湖

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