真菌芳香聚酮化合物的合成生物学研究进展*

真菌芳香聚酮化合物是由真菌非还原聚酮合酶(NR-PKSs)催化形成的具有广泛生物活性的一类天然产物。大部分内源真菌菌株存在难培养、致病性或产率低等问题,从根本上限制了真菌芳香聚酮化合物的开发和应用。随着合成生物学和代谢工程的发展,很多具有生物活性的聚酮产物实现了在工业微生物(如酿酒酵母、构巢曲霉等)中的异源生产,相关研究逐渐成为热点。从合成途径解析与挖掘、底盘细胞的构建与改造等方面综述了近年来真菌芳香聚酮化合物的合成生物学研究进展,为未来真菌芳香聚酮化合物人工代谢途径的高效构建和实现工业化生产奠定基础。     

真菌聚酮化合物生物合成研究进展

具有广泛生物活性的真菌聚酮化合物因具有复杂的化学结构,其生物合成途径一般包含多样且新颖的酶催化反应。文中主要综述了2013-2016年来源于还原性聚酮合成酶(HR-PKSs)、非还原性聚酮合成酶(NR-PKSs)、聚酮-非核糖体多肽合成酶(PKS-NRPSs)和还原性-非还原性聚酮合成酶(HR-NR PKSs)杂合型等四大类型的真菌聚酮类化合物的生物合成研究进展。众多真菌聚酮类化合物生物机理的阐明,为未来新型真菌聚酮类天然产物生物合成基因簇的挖掘、新结构化合物的发现及其类似物的研究提供了方向和理论基础。     

脂肪酸代谢途径影响聚酮化合物生物合成的机制及应用研究进展

聚酮化合物（PKs）作为一大类次级代谢产物，有着重要的生物活性和潜在的应用价值。链霉菌具有合成多种聚酮化合物的潜力，但野生型菌株合成聚酮化合物的产量难以满足工业化生产的需求。贮藏脂质的降解能为聚酮化合物生物合成提供大量的酰基CoA前体，因此，控制好脂肪酸与聚酮化合物生物合成通量，有利于促进目标聚酮化合物的合成。本文综述了强化脂肪酸β-氧化途径提高聚酮化合物产量的研究进展，为利用β-氧化途径促进聚酮化合物生物合成提供了新的研究策略。     

链霉菌中高效生产聚酮化合物的研究方法及进展北大核心CSCD

聚酮化合物是通过聚酮合成途径产生的一大类结构和生物活性多样的次级代谢产物,是链霉菌产生的主要次级代谢产物,具有重要的经济价值。为了在链霉菌中提高聚酮化合物产量,以满足工业生产需求,近年来,代谢工程的方法被广泛应用,例如,过表达合成途径中限速酶或途径特异性激活蛋白、强化前体供应、去除产物反馈抑制、合成基因簇异源表达等。本文将从代谢工程改造实例入手,全面综述链霉菌中聚酮化合物高效生物合成的研究方法及进展,并对利用合成生物学策略智能动态适配各个相关途径,进而提高该类化合物产量的研究思路进行展望。     

聚酮类化合物生物合成的代谢工程研究进展

聚酮化合物是一类重要的具有生物活性的次级代谢物。本文讨论了以聚酮生物合成酶为核心的聚酮化合物生物合成途径,以及近年来有关代谢工程在聚酮类化合物生物合成方面的研究工作进展,主要包括将聚酮生物合成途径引入新的宿主、代谢流量分析在提高聚酮化合物中的应用及合成新的聚酮化舍物等。     

真菌聚酮合酶基因分离方法的研究进展

真菌聚酮合酶在代谢中可催化合成多种具有重要生物学活性的次级代谢物,所以真菌聚酮合酶正逐渐成为药学、食品科学和农学等领域的研究热点。本文综述了近五年来建立的几种分离真菌聚酮合酶基因的方法。这些方法解决了真菌中聚酮合酶基因簇难以分离的问题,为改造和利用真菌聚酮合酶以及发掘真菌聚酮化合物资源提供了强有力的手段。     

异源生物合成聚酮化合物的研究进展

聚酮是一大类具有重要生物活性的天然产物,其生物合成途径复杂多样。利用异源宿主合成聚酮化合物要比使用天然生产菌有很多优点。异源宿主的选择是异源生物合成聚酮的关键。这种宿主必须能够大量表达大分子聚酮合成酶(300 kDa或更大)且能够大规模的转译后修饰这些蛋白;还要能够形成大量的像丙二酰CoA、甲基丙二酰CoA等细胞内起始单元。随着各种技术的不断进步,异源宿主很可能成为大规模生产聚酮化合物的一个强有力平台。本文对聚酮合成酶,异源生产聚酮的优点、条件和应用都有所阐述。     

真菌中PKS-NRPS杂合天然产物研究进展

真菌聚酮合酶-非核糖体多肽合成酶(PKS-NRPS)由于聚合两大主要催化模块PKS与NRPS,能够催化结合来源广泛的聚酮骨架和氨基酸生成结构丰富多样和生物活性广泛的天然产物.本文对2013年至2019年4月真菌来源的14个PKS-NRPS基因及其对应的72个PKS-NRPS杂合天然产物的化学结构、生物活性及生物合成进行总结和论述,并对目前为止报道的所有26个PKS-NRPS基因的同源性及与化合物结构之间的相关性进行分析和讨论,为真菌PKS-NRPS类天然产物及其生物合成研究提供参考.     

真菌苯二酚内酯聚酮类化合物生物合成研究进展

真菌苯二酚内酯类聚酮化合物具有抗癌和调节免疫系统等重要的生物活性,其生物合成是近年来的研究热点。介绍了苯二酚内酯的双聚酮合酶协作合成机制和组合生物合成,并以几种真菌苯二酚内酯生物合成途径为例,综述了相关的研究进展,以期为研究者提供参考。     

植物类型III聚酮合酶超家族基因结构、功能及代谢产物

植物聚酮类化合物主要包括酚类、芪类及类黄酮化合物等,在植物花色、防止紫外线伤害、预防病原菌、昆虫危害以及作为植物与环境互作信号分子方面行使着重要的生物学功能。该类化合物具有显著多样的生物学活性,对人体保健及疾病治疗有显著意义。植物类型III 聚酮化合物合酶 (PKS) 在该类化合物生物合成起始反应中行使着关键作用,决定该类化合物基本分子骨架建成和代谢途径碳硫走向,为合成途径关键酶和限速酶。以查尔酮合酶为原型酶的植物类型III PKS超家族是研究系统进化和蛋白结构与功能关系的模式分子家族,目前已经分离得到14种植物类型III PKS基因,这些同祖同源基因及其表达产物既有共性,也表现出许多独特个性,这些个性赋予此类次生代谢产物结构上的多样性。以下综述了植物类型III PKS超家族基因结构、功能及代谢产物研究进展。     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.