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Synthetic and Systems Biotechnology 2018年第4期3卷 275-282页

作者： keqiang fan Qian Zhang State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing100101People's Republic of China University of Chinese Academy of Sciences Beijing100049People's Republic of China

Angucyclines are one of the largest families of aromatic polyketides with various chemical structures and *** of studies have made it easy for us to depict the picture of their early biosynthetic *** families of oxygenases,the FAD-dependent oxygenases and the ring opening oxygenases,contribute to the formation of some unique skeletons of atypical *** FAD-dependent oxygenases involved in the biosynthetic gene clusters of typical angucyclines catalyze two hydroxylation reactions at C-12 and C-12b of prejadomycin,while their homolog JadH in jadomycin gene cluster catalyze the C-12 hydroxylation and 4a,12b-dehydration reactions of prejadomycin,which leads to the production of dehydrorabelomycin,a common intermediate during the biosynthesis of atypical *** opening oxygenases of a unique family of oxygenases catalyze the oxidative CeC bond cleavage reaction of dehydrorabelomycin,followed by different rearrangement reactions,resulting in the formation of the various chemical skeletons of atypical *** results suggested that the functional differentiation of these oxygenases could apparently enrich the sources of aromatic polyketides with greater structure diversities.

关键词： Angucycline Biosynthesis Oxygenase FAD-dependent monooxygenase Ring opening oxygenase

Tetracycline natural products:discovery,biosynthesis and engineering

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Chinese Journal of Natural Medicines 2022年第10期20卷 773-794页

作者： WANG Haiyan WANG Ljun fan keqiang PAN Guohui State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBeijing 10010lChina University of Chinese Academy of Sciences Beijing 100049China

Tetracycline(TC)natural products possess a variety of remarkable bioactivities and diverse *** are an important and fertile source for developing novel *** one of the most successful drug families,TC antibiotics have been in clinical use for over seven decades,and continue to make an important contribution to human health *** date,studies on TC natural products and their biosynthesis have revealed numerous novel biochemical mechanisms and regulatory elements,which facilitates the rational metabolic engineering studies for generating novel bioactive TC analogs and inspires the development of new synthetic biology *** this review,we provide a comprehensive overview on the discovery,biosynthesis,and engineering of the existing TC natural *** analyses will be of great value for the discovery,design and development of novel TC drugs in the future.

关键词： Tetracycline Polyketide synthases Biosynthesis Engineering

Regulatory perspective of antibiotic biosynthesis in Streptomyces

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Science China(Life Sciences) 2019年第5期62卷 698-700页

作者： Hanzhi Yin Weishan Wang keqiang fan Zilong Li State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences School of Life Science Hunan University of Science and Technology

Streptomycetes are Gram-positive bacteria with high GC DNA content. They produce the most abundant secondary metabolites including over two-thirds of the clinically used antibiotics of natural origin (Barka et al., 2016), for example,the important broad-spectrum antimicrobials oxytetracycline(OTC) and chlortetracycline, which are the tetracycline antibiotics。

关键词： Regulatory perspective of antibiotic biosynthesis in Streptomyces

Improvement of oxytetracycline production mediated via cooperation of resistance genes in Streptomyces rimosus

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Science China(Life Sciences) 2017年第9期60卷 992-999页

作者： Shouliang Yin Xuefeng Wang Mingxin Shi fang Yuan Huizhuan Wang Xiaole Jia fang Yuan Jinliang Sun Tiejun Liu Keqian Yang Yuxiu Zhang keqiang fan Zilong Li State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of Sciences Department of Environmental and Biological Engineering School of Chemical and Environmental EngineeringChina University of Mining and Technology(Beijing) Shengxue Dacheng Pharmaceutical Co. Ltd

Increasing the self-resistance levels of Streptomyces is an effective strategy to improve the production of *** increase the oxytetracycline(OTC) production in Streptomyces rimosus,we investigated the cooperative effect of three co-overexpressing OTC resistance genes:one gene encodes a ribosomal protection protein(otrA) and the other two express efflux proteins(otrB and otrC).Results indicated that combinational overexpression of otrA,otrB,and otrC(MKABC) exerted a synergetic *** production increased by 179%in the recombinant strain compared with that of the wild-type strain *** resistance level to OTC was increased by approximately two-fold relative to the parental strain,thereby indicating that applying the cooperative effect of self-resistance genes is useful to improve OTC ***,the previously identified cluster-situated activator OtcR was overexpressed in MKABC in constructing the recombinant strain MKRABC;such strain can produce OTC of approximately7.49 g L^((-1)),which represents an increase of 19%in comparison with that of the OtcR-overexpressing strain *** work showed that the cooperative overexpression of self-resistance genes is a promising strategy to enhance the antibiotics production in Streptomyces.

关键词： resistance genes oxytetracycline combinatorial overexpression cluster-situated activator Streptomyces rimosus

Tackling the microlensing wave effects of strong lensing gravitational waves with TAAH

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 257-258页

作者： Zuhui fan South-Western Institute for Astronomy Research Yunnan University

The rapid development of gravitational wave（GW） observations since their first detection in 2015 [1] has opened a completely new window for exploring the Universe. Consequently, astronomical research has entered the multimessenger era, allowing us to use different tracers to view the cosmos from various perspectives. Among others, the appealing application of gravitational wave events from compact binary mergers is that they can act as standard sirens to determine absolute cosmic distances entirely independent of standard candles. This approach is one of the most promising means to solve the current H0tension problem.

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糖丝菌属次级代谢潜能分析及代表菌株基因编辑体系建立

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微生物学通报 2024年第7期51卷 2614-2629页

作者：李栋范可强胡会涛潘国辉中国科学院微生物研究所微生物资源前期开发国家重点实验室北京100101 中国科学院大学存济医学院北京101408

【背景】稀有放线菌是发掘天然产物的“新矿藏”。糖丝菌(Saccharothrix)作为典型的稀有放线菌,其天然产物生产潜能尚需进行系统分析和发掘。此外,针对糖丝菌的基因编辑体系也鲜有报道。【目的】揭示糖丝菌属稀有放线菌合成不同结构类... 详细信息

【背景】稀有放线菌是发掘天然产物的“新矿藏”。糖丝菌(Saccharothrix)作为典型的稀有放线菌,其天然产物生产潜能尚需进行系统分析和发掘。此外,针对糖丝菌的基因编辑体系也鲜有报道。【目的】揭示糖丝菌属稀有放线菌合成不同结构类型天然产物的潜能,并建立代表菌株的基因编辑体系,推动新结构天然产物发现及相关生物合成研究。【方法】通过多位点序列分析(multi-locus sequence analysis,MLSA)方法评价已公布的34个糖丝菌基因组之间的相似度,利用antiSMASH分析基因簇及其合成产物的结构信息,并使用BiG-SCAPE对基因簇进行聚类分析。选择代表菌株澳大利亚糖丝菌(Saccharothrix australiensis)DSM43800和紫丁香糖丝菌(Saccharothrix syringae)NRRL B-16468,以整合型载体和基因敲除载体为工具,建立接合转移及基因编辑体系。【结果】对34个糖丝菌基因组的分析显示,共发现了1348个天然产物生物合成基因簇,平均每个基因组含有约40个基因簇。其中,合成聚酮、非核糖体肽、聚酮-非核糖体肽杂合产物,以及核糖体合成和翻译后修饰肽类天然产物的基因簇丰度较高。这1348个基因簇聚类成852个基因簇家族(gene cluster family,GCF),进一步聚集成130个基因簇集团(gene cluster clan,GCC)。本研究建立并优化了适用于澳大利亚糖丝菌和紫丁香糖丝菌的接合转移操作体系,并建立了2个代表菌株的基因编辑体系,获得了相应的突变菌株。【结论】糖丝菌作为稀有放线菌,其基因组内富含天然产物生物合成基因簇,展现出合成众多结构类型天然产物的强大潜能,尤其是聚酮与聚肽类天然产物。我们成功实现了对糖丝菌基因组的精准编辑,为深入研究基因簇及其合成的天然产物奠定了坚实的基础。

关键词：糖丝菌次级代谢天然产物生物合成基因簇基因编辑

Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： Andrew Gregory Chengyun Tang fan fan Department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(AD)and Alzheimer's diseaserelated dementias(ADRD)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,AD/ADRD has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

高浓度底物下青霉素扩环酶的活性评价与底物抑制现象

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生物工程学报 2015年第12期31卷 1690-1699页

作者：伍林军范可强季俊杰杨克迁中国科学院微生物研究所微生物资源前期开发国家重点实验室北京100101 中国科学院大学北京100049

本文对青霉素扩环酶(Penicillin expandase,也称Deacetoxycephalosporin C synthase,DAOCS)在高浓度青霉素G下的底物抑制现象进行初步评价与表征,筛选适合工业应用条件的高活力突变体。我们通过HPLC对已报道的几个DAOCS高活力突变体在... 详细信息

本文对青霉素扩环酶(Penicillin expandase,也称Deacetoxycephalosporin C synthase,DAOCS)在高浓度青霉素G下的底物抑制现象进行初步评价与表征,筛选适合工业应用条件的高活力突变体。我们通过HPLC对已报道的几个DAOCS高活力突变体在青霉素G浓度5.6至500 mmol/L间的比活力进行定量测定,并与不同催化反应动力学模型的理论推测变化趋势比较,发现DAOCS野生型酶及高活力突变体H4、H5、H6与H7在高浓度青霉素G条件下均表现出明显的底物抑制现象,但是变化趋势不同。野生型酶与突变体H4的比活力先上升后下降,与竞争性抑制模型预测不符。突变体H5、H6与H7的比活力变化呈现更复杂的变化趋势。在所有测试的突变体中,H6的活性显著高于其他突变体酶。青霉素G对野生型DAOCS的底物抑制现象符合非竞争性抑制模型的预测。而部分突变体表现出复杂的底物抑制行为,表明其具有更复杂的作用机制。在高底物浓度下筛选具有较强催化活性的青霉素扩环酶突变体对于推动其在工业生产中的应用具有重要指导作用。

关键词：去乙酰氧头孢菌素C合成酶底物抑制高浓度青霉素G

Reconstructing forest and grassland cover changes in China over the past millennium

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Science China Earth Sciences 2025年第1期68卷 94-110页

作者： fanneng HE fan YANG Yafei WANG Key Laboratory of Land Surface Pattern and Simulation Institute of Geographic Sciences and Natural Resources Research Chinese Academy of Sciences Key Research Institute of Yellow River Civilization and Sustainable Development Henan University University of Chinese Academy of Sciences

Historical forest and grassland cover changes not only are critical indicators for quantifying ecological and environmental change processes but also serve as fundamental data for long-term climate change simulations and terrestrial ecosystem carbon emission assessments. However, because of limitations in historical data, quantitative estimations and spatially gridded reconstructions of these changes remain challenging, necessitating further methodological exploration. This study focused on China's present-day land area over the past millennium, objectively capturing the characteristics and drivers of forest and grassland cover changes. On this basis, using the forest transition theory and the space-for-time substitution method, we depicted the historical deforestation process as an inverted “S” curve and developed a model to reconstruct historical forest area changes based on the functional relationship between the forest area and population size dynamics. Subsequently, a gridded forest allocation model was established on the basis of deforestation tendencies. For the grassland cover, we implemented regionspecific methods, such as the cropland area deduction method and the habitat constraint method, to quantitatively reconstruct historical changes. Consequently, we obtained provincial forest and grassland area changes over the past millennium and mapped 10-km-resolution gridded data of forest and grassland cover. The results indicated the following.(1) The methods developed using population data as a proxy objectively reproduced the spatiotemporal evolution of forest and grassland cover in China over the past millennium. These feasible methods offer a novel pathway for the quantitative reconstruction of historical forest and grassland cover changes.(2) The data indicated that China's forest area generally decreased over the past millennium, characterized by a “decrease-then-increase” pattern. The forest area experienced three distinct phases: a slow decline(AD 1000

关键词： Land use and land cover change Forest Grassland Quantitative reconstruction Gridded reconstruction China historical period

芳香聚酮早期后修饰环化酶的结构分类和功能分析

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微生物学报 2010年第5期50卷 561-567页

作者：张霞范可强李红玉杨克迁兰州大学生命科学学院兰州730000 中国科学院微生物研究所微生物资源前期开发国家重点实验室北京100101

聚酮是一类结构和生物活性多样的天然产物,根据结构特点可以分为芳香聚酮和复合聚酮两大类。芳香聚酮环化酶是芳香聚酮生物合成过程中一种非常重要的早期后修饰酶,是决定芳香聚酮骨架结构的主要影响因素。根据序列和结构的相似性,芳香... 详细信息

聚酮是一类结构和生物活性多样的天然产物,根据结构特点可以分为芳香聚酮和复合聚酮两大类。芳香聚酮环化酶是芳香聚酮生物合成过程中一种非常重要的早期后修饰酶,是决定芳香聚酮骨架结构的主要影响因素。根据序列和结构的相似性,芳香聚酮环化酶可以分为不同的种类。本文主要对其中3类芳香聚酮环化酶结构和功能进行了简要总结,从晶体结构、催化反应和催化机制等方面对它们进行了分类描述和功能分析,并结合自己实验室工作介绍了杰多霉素B环化酶催化机制的研究方法。

关键词：聚酮后修饰酶环化/芳化酶晶体结构催化机制