丝状真菌新型全局性调控因子LaeA

全局调控在丝状真菌次级代谢调控及其生长发育过程中有着重要的作用。LaeA是2004年首次在构巢曲霉中被发现的第一个丝状真菌全局性调控因子,继而在烟曲霉、黄曲霉、产黄青霉、橘青霉中相继被报道。LaeA能够全局性调控抗生素和真菌毒素等次级代谢产物的合成,影响真菌形态分化,另外还通过影响沉默基因的表达从而调控未知代谢产物的产生,因而能为真菌中天然产物的开发提供新的重要途径。本文就其在丝状真菌中的发现、功能、作用机制及其应用等方面进行综述。     

LaeA在丝状真菌次级代谢、生长发育和其他重要生物过程中的作用

LaeA是在构巢曲霉中首次鉴定的一种全局调控因子,其同源蛋白在丝状真菌中广泛存在,具有高度的保守性。LaeA及其同源蛋白序列存在S-腺苷甲硫氨酸结合基序,是一种甲基转移酶,可能影响组蛋白修饰,导致染色体结构的改变,进而调控一系列基因的表达。大量研究表明,LaeA及其同源蛋白参与调控丝状真菌多种次级代谢产物的生物合成,影响丝状真菌的生长发育和形态分化,甚至在丝状真菌生产有机酸和一些工业酶的过程中也发挥着重要作用。本文综述了LaeA及其同源蛋白的作用机制,以及该蛋白在丝状真菌次级代谢、生长发育和其他重要生物过程中的作用,并对存在的问题及应用前景进行讨论与展望。     

Motif-Independent Prediction of a Secondary Metabolism Gene Cluster Using Comparative Genomics: Application to Sequenced Genomes of Aspergillus and Ten Other Filamentous Fungal Species

Despite their biological importance, a significant number of genes for secondary metabolite biosynthesis (SMB) remain undetected due largely to the fact that they are highly diverse and are not expressed under a variety of cultivation conditions. Several software tools including SMURF and antiSMASH have been developed to predict fungal SMB gene clusters by finding core genes encoding polyketide synthase, nonribosomal peptide synthetase and dimethylallyltryptophan synthase as well as several others typically present in the cluster. In this work, we have devised a novel comparative genomics method to identify SMB gene clusters that is independent of motif information of the known SMB genes. The method detects SMB gene clusters by searching for a similar order of genes and their presence in nonsyntenic blocks. With this method, we were able to identify many known SMB gene clusters with the core genes in the genomic sequences of 10 filamentous fungi. Furthermore, we have also detected SMB gene clusters without core genes, including the kojic acid biosynthesis gene cluster of Aspergillus oryzae. By varying the detection parameters of the method, a significant difference in the sequence characteristics was detected between the genes residing inside the clusters and those outside the clusters.     

Chemistry and Bioactivities of Secondary Metabolites from the Genus Talaromyces

Fungi have especially captured the interest and fascination of natural product chemists in that they produce a dizzying array of natural organic molecules with many unique functional groups and atom arrangements. In this review, we focus on the genus Talaromyces (Trichocomaceae) which has been a hot spot of natural product studies over the last three decades. This review summarized the discovery, structures, and bioactivities of various classes of 151 compounds isolated from both terrestrial and marine derived fungal strains of the genus Talaromyces reported from 1994 to 2019.     

中国海洋共附生真菌次生代谢产物最新研究进展

我国海洋共附生真菌研究起步较晚,近年来取得大量有价值的成果,本文主要综述我国海洋共附生真菌次生代谢产物结构和生理活性研究中的最新进展.     

丝状真菌次级代谢产物的研究现状与发展趋势

近年来,丝状真菌次级代谢产物的研究在国内外受到了极高的重视,同时也取得了较大的进展。本文对丝状真菌次级代谢产物的生物合成和调控机制以及隐性次级代谢产物生物合成基因簇的激活等方面进行了简述,同时对组合生物学给真菌次级代谢产物研究带来的机遇和挑战进行了讨论。     

海洋真菌Arthrinium sp. UJNMF0008代谢产物的研究

为丰富海洋真菌的化学多样性,发现海洋真菌活性代谢产物,对海洋沉积物来源真菌Arthriniumsp.UJNMF0008的化学成分及其生物活性进行研究,采用硅胶柱色谱、凝胶柱色谱、反向柱色谱和高效液相色谱等方法从海洋沉积物来源真菌Arthriniumsp.UJNMF0008的发酵提取物中分离到5个化合物,通过核磁共振、质谱等方法,结合文献对照,鉴定了化合物的结构分别为arthoneF(1)、arthoneG(2)、sydoxanthoneC(3)、(3R,4R)-cis-4-hydroxymellein(4)和2-(2′S-hydroxypropyl)-5-methyl-7-hydroxychromone(5),其中化合物1和2是新化合物,化合物3首次从该属真菌中分离到。活性测试显示,化合物1~5在50μmoL/L的测试浓度下均没有表现出明显的抗氧自由基活性、抗菌活性以及NO释放抑制活性。     

杜比亚蟑螂共生真菌次生代谢产物及其生物活性

为探究杜比亚蟑螂体内共生真菌种类,测定共生真菌次生代谢产物的抑菌活性和抗氧化活性,筛选出具有抗菌和抗氧化活性的菌株,本研究采用组织块分离法分离杜比亚蟑螂体内的共生真菌,通过形态学和分子生物学相结合的方法对分离到的共生真菌进行鉴定;分别采用薄层层析-生物自显影法和DPPH法测定共生真菌次生代谢产物的抗细菌活性和抗氧化活性。结果表明,从杜比亚蟑螂体内共分离鉴定得到5种不同的共生真菌,主要分布于青霉属(1株)、曲霉属(3株)和聚孢霉属(1株)。活性测定的结果表明,菌株Bdf-2、Bdf-4和Bdf-5表现出较好的抗菌活性,且菌液提取物的抗菌活性要强于菌丝。Bdf-1,Bdf-2和Bdf-3菌液次生代谢产物表现出抗氧化活性,IC 50值分别为0.26 mg/mL、2.20 mg/mL和0.75 mg/mL。杜比亚蟑螂共生真菌以青霉属和曲霉属为主,且具有抗菌和抗氧化活性的次生代谢产物主要分布于菌液中。     

海洋真菌Penicillium sp. WP-13次级代谢产物研究

本研究分析了海洋真菌Penicillium sp. WP-13的活性次级代谢产物。采用多种柱色谱技术对其发酵液的乙酸乙酯提取物进行分离纯化;根据波谱数据和理化常数分析,并结合文献比对鉴定单体化合物的结构;采用MTT法测定化合物对肿瘤细胞的细胞毒活性。从Penicillium sp. WP-13发酵液的乙酸乙酯提取物中分离鉴定了5个单体化合物,其中2个内酯类化合物为1-hydroxy-3,10-dimethoxy-8-methyl-6,11-dioxo-6,11-dihydrodibenzo[b,e]oxepine-9-carboxylicacid(1)和1,8-dihydroxy-10-methoxy-3-methyl-dibenzo[b,e]oxepine-6,11-dione(2); 3个蒽醌类化合物为endocrocinmethylester(3)、2-chloro-1,3,8-trihydroxy-6-methyl-9,10-anthracenedione (4)和emodin (5)。活性测试结果显示,化合物3和5均对人慢性髓原白血病细胞株K562、人肝癌细胞株BEL-740...     

药用真菌活性次级代谢产物研究

药用真菌作为我国传统中医药体系的重要组成部分,有着悠久的历史。它们能够产生丰富的活性次级代谢产物,具有神经保护、抗肿瘤、降血脂等诸多药效。然而,目前对大部分药用真菌次级代谢产物的化学和生物学研究较少。本课题组主要以抗肿瘤、抗炎、抗菌以及抗病毒等生物活性为指导,选择重要药用真菌进行化学研究,构建我国特色药用真菌代谢产物库。文章主要介绍近4年我们在这方面的研究进展。     

低温型真菌抗肿瘤活性次级代谢产物研究进展

真菌栖息生境及物种的多样性使其次级代谢产物化学结构和生物活性呈多样性特点,结构与功能多样的真菌次级代谢产物已成为新药先导化合物发现的重要资源。低温型真菌因其独特而恶劣的生存环境进化出特有的适冷特性及代谢途径,使其产生结构新颖、活性显著的次级代谢产物的几率大大提升,已成为药物研发的热点领域。近年来,研究者陆续从高海拔地区、南北极地和深海地带等低温生境分离鉴定出上百种结构新颖的次级代谢产物,并显示出抗肿瘤、抗菌、抗病毒和免疫调节等多种活性。本文对近10年来源于上述生境的低温型真菌抗肿瘤活性次级代谢产物的研究进展进行综述,为其用于创制抗肿瘤新药提供新思路。     

深海真菌多样性及其代谢产物生物活性的研究进展

深海环境复杂多样,深海微生物逐渐进化以适应其生存环境。真菌作为深海环境中的重要微生物类群,是开发海洋生物的新兴资源。综述了近年来深海真菌的物种多样性、活性代谢产物的多样性及其生物学功能等的研究进展,并对未来深海真菌的应用进行了展望。     

Heteroatom-Containing Antibacterial Phenolic Metabolites from a Terrestrial Ampelomyces Fungus

Two new sulfur-containing phenolic compounds, 7-hydroxy-5-hydroxymethyl-2H-benzo[1,4]thiazin-3-one (1) and 2,5-dihydroxy-3-methanesulfinylbenzyl alcohol (2), along with two known compounds, 3-chloro-2,5-dihydroxybenzyl alcohol (3) and 2-hydroxy-6-methylbenzoic acid (4), were isolated from the mycelial solid culture of a soil-derived Ampelomyces fungus by antibacterial assay-guided fractionation. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1–3 showed structure and microbial dependent antibacterial activities.     

Secondary metabolites from Mycosphaerella ligulicola

(+)-Epoxydon, together with the new (+)-epoxydon monoacetate, 3-methylidene-6-methoxy-1,4-benzodioxan-2-one and 2-(2-hydroxy-5-methoxyphenoxy)-acrylic acid, has been isolated and identified from the mycelium of Mycosphaerella ligulicola grown on Sabouraud-maltose 4 %-agar.     

Cadmium removal capacities of filamentous soil fungi isolated from industrially polluted sediments,in La Plata (Argentina)

Aspergillus terreus, Cladosporium cladosporioides, Fusarium oxysporum, Gliocladium roseum, Penicillium spp., Talaromyces helicus and Trichoderma koningii were isolated from heavily polluted streams near an industrial area in La Plata, Argentina. The fungi were obtained from sediments with 0.25–0.50 mg Cd/l and they were isolated in cadmium-basal medium. They were then cultivated to evaluate their Cd detoxification abilities. The biomass developed in static assays represented 5–53% of the yield of stirred cultures, for the different fungal species, although the cadmium absorption were similar in both cases. These soil fungi represented 50% of the total isolates and their mycelial growth was conspicuous in these polluted sediments. Although bacteria have been mentioned as active microorganisms against heavy metals, the mycelial fungi were able to develop a significantly higher mass to sequestrate more metals. Thus, they could be used in remediation biotechnology to improve the Cd detoxification of chronically contaminated habitats.     

粘细菌次生代谢产物中大环类化合物的研究进展

粘细菌可以产生多种次生代谢产物,是继放线菌、芽胞杆菌之后的第3大类次级代谢产物产生菌。本文综述了粘细菌次生代谢产物中大环类化合物的研究进展。首先介绍了粘细菌中分离的主要大环类化合物种类、结构特征及来源菌株;然后分别从抗肿瘤、抗菌、抗病毒等几方面对其生物活性进行概述;最后对粘细菌次生代谢产物中大环类化合物的相关研究工作进行了展望。     

栎生桑黄和忍冬桑黄液体培养过程中发酵液抗氧化能力

桑黄孔菌属Sanghuangporus是药用木生真菌资源中一个重要的属,但是该属仅有少数几个种类被用于人工栽培,且栽培面积较小。此外,桑黄孔菌属中大部分种类的药用功能仍未完全明确。因此,本研究以桑黄孔菌属近期新发表的新种栎生桑黄S. quercicola和关注度较低的忍冬桑黄S. lonicericola为主要研究对象,通过测定它们液体培养过程中第2、4、6、8、10、12和14天的菌丝生物量以及发酵液的粗多糖含量、多酚含量、黄酮含量、抗坏血酸含量、DPPH自由基清除能力、ABTS自由基清除能力、总抗氧化能力、超氧化物歧化酶活性、羟自由基清除能力、超氧阴离子清除能力、铁离子还原能力和亚铁离子螯合能力等12个抗氧化指标,对桑黄的抗氧化能力进行评定。2种桑黄真菌各选取一号菌株,其发酵液均表现出强抗氧化能力。相比之下,栎生桑黄的多糖、抗坏血酸和超氧化物歧化酶含量更高,而忍冬桑黄的多酚和黄酮含量更高。相应的,栎生桑黄和忍冬桑黄在其他一些抗氧化指标上也表现出强弱程度及出现时间的差异。上述研究结果为桑黄孔菌属真菌的药用功能开发提供了新资源,为不同抗氧化代谢产物的分离纯化提供了科学依据。     

Secondary Metabolites from Marine Micromonospora: Chemistry and Bioactivities

Marine Micromonospora was revealed to be a rather untapped and a rich source of chemically diverse and unique bioactive natural products. This review is aimed to make a comprehensive survey of secondary metabolites that were derived from marine Micromonospora including chemical diversity and biological activities. A total of 116 compounds from 41 marine Micromonospora species have been reported, covering the literatures from 1997 to 2019. These compounds contain several structural classes such as polyketides (PKS), nonribosomal peptides (NRPS), PKS‐NRPS hybrids, terpenes and others, and they present cytotoxic, antibacterial, antiparasitic, chemopreventive or antioxidant activities.     

丝状真菌杀松材线虫代谢产物研究进展

松材线虫病是破坏我国森林生态系统最为严重的病害,具有极强的传播性和破坏性,防治此种病害迫在眉睫。基于对物理和化学方式防治松材线虫的研究,对环境友好度最高的生物防治具有更广的研究前景。丝状真菌及其次级代谢产物,来源于自然,与传统的化学杀线虫药剂相比,对环境影响较小,针对松材线虫的致死作用更为专一,因此,从丝状真菌的次级代谢产物中分离获得杀松材线虫活性产物并测定其结构和活性,对于松材线虫病的防治具有重要意义。本文对丝状真菌产生的具有杀松材线虫活性产物的结构、活性展开综述,发现近二十年共有57个活性产物被发现,且结构多种多样,活性差别较大,为了更好地开展此领域的研究,本文对所有产物的结构和活性进行了系统总结,最后又对该领域的研究进行了总结和展望,以期对松材线虫病的生物防治和丝状真菌杀松材线虫次级代谢产物的深入研究提供参考。