右旋糖酐酶研究进展

右旋糖酐酶是一种将高分子右旋糖酐催化降解为低分子量多糖的水解酶。该酶及其催化产物在医药、食品、化工等工业领域具有重要的应用价值与广泛的工业用途,因此近年来国内外对右旋糖酐酶的研究逐渐增多。结合文献记载及本实验室研究成果,对右旋糖酐酶的研究进展及其工业应用进行综述,并对当前有关该酶研究的热点和重点、国内右旋糖酐酶研究存在的问题以及未来的研究趋势提出了见解。     

固定化生物催化剂的研究动向

近年来,国内外对于固定化酶、固定化细胞、固定化细胞器以及生物传感器的研究很活跃,在固定化方法上取得了较大进展,一部分固定化酶、固定化微生物细胞以及生物传感器在食品发酵工业、有机合成工业、化学分析、临床诊断以及能源开发等方面得到了应用。目前,大多数固定化酶、固定化细胞以及生物传感器还处在实验室研究阶段或中试阶段,有待改进;动物细胞、植物细胞以及细胞器的固定化研究还处于探索阶段、有待深入。     

基因工程改良淀粉品质

淀粉对人类生活十分重要,它不仅是人们的能量和营养来源,而且还是重要的工业原材料。对于淀粉合成过程及淀粉的加工、使用一直是淀粉研究的重点内容。淀粉的合成在最后阶段涉及到３个关键性的酶是：ＡＤＰＧ焦磷酸化酶、淀粉合成酸以及淀粉分支酶。它们分别催化ＡＤＰ－葡萄糖的形成、葡聚糖链的延伸以及分支链的形成。另外淀粉去分支酶对淀粉最终结构的形成也起到重要作用。本文将介绍上述４个酶近年来的生物化学和分子生物学研究     

工业酶的现状和未来发展

应用工业酶往往能给最终产品制造商带来诸多好处,包括降低能耗、减少成本、产生更少废物等,正是由于具有这些优势,近年来在工业生产中,工业酶的应用越来越广泛.尽管如此,工业酶市场的发展也面临着不少的挑战.特别是产品生命周期已处于成熟和衰退阶段的工业酶市场面临销售下滑的局面.正因为如此,技术的更新以及新的应用领域的开拓将引领工业酶市场的发展.为此,我们特别邀请了杜邦工业生物科技事业部亚太应用中心总监段钢博士,以连载的形式,对工业酶制剂以及酶技术的开发进行解读,并介绍工业酶在淀粉生产和淀粉深加工、生物燃料、生化品的生产、食品和饲料及纺织和洗涤等方面的应用,以期读者对工业酶的开发和应用情况有一个更深入的了解     

工业环境下酶蛋白的催化行为与适应性改造研究进展

酶在工业上有着广泛应用和巨大潜力,但工业生产中高温、强酸/碱、高盐、有机溶剂和高底物浓度等条件仍然制约着酶的大规模应用。为使酶能更好地在工业环境下发挥催化作用,目前的主要策略是对酶进行适应性改造(如理性或半理性设计、定向进化、固定化等)。文中简要阐述了酶在工业环境下的催化行为以及近年对其适应性改造的研究进展,以期为酶的适应性改造提供参考。     

蛋白质酶功能分析和预测方法的进展和前瞻

蛋白质酶是生物体内最重要的生物分子之一。对酶的功能进行系统研究具有重要的科学研究价值和工业应用意义,近年来,以计算机技术为基础的酶功能预测的方法不断发展与完善。基于此背景,本文总结了基于计算方法的酶功能分析与预测的主要方法,包括酶结合位点、分子对接、动力学模拟以及分子设计等内容。同时,本文也对相应的发展趋势进行讨论和展望。     

工业生物技术：工业可持续发展最有希望的技术——欧阳平凯院士访谈

——请您简单介绍一下目前工业生物技术发展现状与发展趋势。欧阳院士：工业生物技术是指在工业规模生产过程中运用微生物或酶为催化剂进行物质加工制造的技术．广泛应用于化工、制药、食品、饲料、轻纺、矿产、材料和能源等工业领域。工业生物技术是生物技术发展史上继医药生物技术、农业生物技术之后的第三次浪潮．对于解决人类社会目前面临的资源、能源与环境等诸多重要问题具有重要意义。     

木霉T6木聚糖酶固态发酵中试生产条件研究

木聚糖酶 (ＸｙｌａｎａｓｅＥＣ .3.2 .1 .8)是一类重要的木糖苷键水解酶 ,对于降解半纤维素起着重要作用[1,2 ] 。该酶在工业上具有巨大的潜在应用价值。在饲料工业上 ,该酶可以提高畜禽对饲料的利用率[3 ] ;在食品工业上 ,该酶的水解产物寡木糖是一类保健食品[4] ,还可用于制备食品增稠剂和澄清果汁 ;在制浆造纸工业上 ,纸浆经过木聚糖酶处理后 ,可降低卡伯值 ,减少含氯漂白剂用量[5 6] ,从而降低环境污染。国外对木聚糖酶的研究起步较早 ,美国、加拿大等发达国家已经进入商品化生产 ,市场需求不断扩大。国内也有对该酶生产的研究 ,但未…     

马克斯克鲁维酵母在工业生物技术中的应用

马克斯克鲁维酵母Kluyveromyces marxianus是目前研究较为广泛的一种非传统酵母,因其耐高温、生长速率快、底物谱广等诸多优势而越来越多地应用于工业生物技术领域。马克斯克鲁维酵母可以分泌菊粉酶、β-半乳糖苷酶等多种应用广泛的水解酶类;还可以利用菊粉类原料、乳清、糖蜜以及木糖等多种非粮底物生产乙醇;其在外源蛋白的分泌以及基因工程操作等工业分子生物学领域也取得了突破。现主要对近年来马克斯克鲁维酵母在产酶、乙醇发酵、分泌外源蛋白等诸多工业生物技术领域的研究进展及存在的挑战进行综述,为进一步推动马克斯克鲁维酵母在工业生物技术中的应用奠定基础。     

工业酶蛋白研究的重要进展

作为生物催化剂的核心,工业酶的研究在近年来取得了许多重要的进展,特别是具有重要意义的新酶发现、酶家族研究、酶的分子改造等领域出现了许多突破性的进展。     

Origin of fatty acid synthesis: Thermodynamics and kinetics of reaction pathways

Summary The primitiveness of contemporary fatty acid biosynthesis was evaluated by using the thermodynamics and kinetics of its component reactions to estimate the extent of its dependence on powerful and selective catalysis by enzymes. Since this analysis indicated that the modern pathway is not primitive because it requires sophisticated enzymatic catalysis, we here propose an alternative pathway of primitive fatty acid synthesis that uses glycolaldehyde as a substrate. In contrast to the modern pathway, this primitive pathway is not dependent on an exogenous source of phosphoanhydride energy (ATP). Furthermore, the chemical spontaneity of its reactions suggests that it could have been readily catalyzed by the rudimentary biocatalysts available at an early stage in the origin of life.     

Sensitivity of pathway rate to activities of substrate-cycle enzymes: application to gluconeogenesis and glycolysis

In a study of metabolic regulation, it is frequently useful to consider the degree to which an enzyme can influence the rate of its pathway. The most productive expression of rate-controlling influence is the fractional change in pathway rate per fractional change in enzyme activity (called control strength or sensitivity coefficient). We have developed a system for considering how a substrate-cycle enzyme's control strength depends on its flux and reaction order and on related features of other enzymes of its pathway. We have applied this system to the gluconeogenic pathway of rat liver and the glycolytic pathway of bovine sperm, where enough fluxes and reaction orders have been published to allow valid estimates of several control strengths. In normal fed animals where gluconeogenesis is slow and unidirectional substrate-to-product and product-to-substrate fluxes are comparable, all substrate-cycle limbs have very high and similar control strengths regardless of their flux rates and positions in the pathway. The activity of a step affects all substrate-cycle control strengths similarly as it affects unidirectional end-to-end fluxes relative to net rate. Control strengths of non-substrate-cycle enzymes are negligible compared to those of substrate cycles. In fasting animals, on the other hand, where unidirectional Pyr----Glc flux is much greater than Glc----Pyr flux, upstream enzymes (near Pyr) have a regulatory advantage over downstream enzymes (near Glc). In this circumstance, control strength of each substrate-cycle enzyme is inversely related to rate limitingness between its substrate and the pathway substrate. Because the Pyr/PEP cycle is significantly rate limiting, the control strength of the Pyr----PEP limb is much greater than that of pyruvate kinase and all downstream enzymes. In the glycolytic pathway of bovine sperm, strong product inhibition of hexokinase detracts greatly from its rate limitingness and control strength, which are very small despite its position at the beginning of the pathway and its large free energy. Because the glucose-transport-hexokinase segment is not rate limiting, phosphofructo 1-kinase has almost as much control strength as it would have as the first enzyme of the pathway, and because the F6P/FDP cycle is only moderately rate limiting, Fru-1,6-P2ase and enzymes further downstream have substantial control strengths. When glycolysis is accelerated by stimulation of phosphofructo 1-kinase, control strength shifts from phosphofructo-1-kinase and all downstream enzymes to the transporthesokinase segment.(ABSTRACT TRUNCATED AT 400 WORDS)     

The Wnt connection to tumorigenesis

Wnt signaling has been identified as one of the key signaling pathways in cancer, regulating cell growth, motility and differentiation. Because of its widespread activation in diverse human tumor diseases, the Wnt pathway has gained considerable and growing interest in tumor research over recent years. Evidence that altered Wnt signaling is important for human tumor development came from three major findings: (i) the tumor suppressor adenomatous polyposis coli (APC) binds to the Wnt pathway component beta-catenin and is involved in its degradation, (ii) mutations of APC in colon tumors lead to stabilization of the beta-catenin protein and (iii) tumor-associated mutations of beta-catenin in colorectal cancer as well as in other tumor types lead to its stabilisation, qualifying beta-catenin as a proto-oncogene. Here we will describe the biochemical interactions which shape the Wnt pathway and focus on its role in tumorigenesis.     

Biphasic estradiol-induced AKT phosphorylation is modulated by PTEN via MAP kinase in HepG2 cells

We reported previously in HepG2 cells that estradiol induces cell cycle progression throughout the G1-S transition by the parallel stimulation of both PKC-alpha and ERK signaling molecules. The analysis of the cyclin D1 gene expression showed that only the MAP kinase pathway was involved. Here, the presence of rapid/nongenomic, estradiol-regulated, PI3K/AKT signal transduction pathway, its modulation by the levels of the tumor suppressor PTEN, its cross-talk with the ERK pathway, and its involvement in DNA synthesis and cyclin D1 gene promoter activity have all been studied in HepG2 cells. 17beta-Estradiol induced the rapid and biphasic phosphorylation of AKT. These phosphorylations were independent of each other, being the first wave of activation independent of the estrogen receptor (ER), whereas the second was dependent on ER. Both activations were dependent on PI3K activity; furthermore, the ERK pathway modulated AKT phosphorylation by acting on the PTEN levels. The results showed that the PI3K pathway, as well as ER, were strongly involved in both G1-S progression and cyclin D1 promoter activity by acting on its proximal region (-254 base pairs). These data indicate that in HepG2 cells, different rapid/nongenomic estradiol-induced signal transduction pathways modulate the multiple steps of G1-S phase transition.     

Emerging role of Hippo signalling pathway in bladder cancer

Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co‐effectors YAP1/TAZ. The core components of the Hippo pathway, which induce BC stemness acquisition, metastasis and chemoresistance, will be emphasized. Additional research on the Hippo pathway will advance our understanding of the mechanism of BC as well as the development and progression of other cancers and may be exploited therapeutically.     

Sphingosine 1-phosphate is a key metabolite linking sphingolipids to glycerophospholipids

The sphingolipid metabolite sphingosine 1-phosphate (S1P) is a well-known lipid mediator. As a lipid mediator, S1P must be present in extracellular space and bind to its cell surface receptors (S1P_1–5). However, most S1P, synthesized intracellularly, is metabolized without being released into extracellular space, in other words, without functioning as a lipid mediator in the vast majority of cells except those supplying plasma and lymph S1P such as blood cells and endothelial cells. Instead, intracellular S1P plays an important role as an intermediate of the sole sphingolipid-to-glycerophospholipid metabolic pathway. The degradation of S1P by S1P lyase is the first irreversible reaction (committed step) of this pathway. This metabolic pathway is conserved in eukaryotes from yeast to human, indicating its much older origin than the function of S1P as a lipid mediator, which is found to be present only in vertebrates and chordates. The sphingolipid-to-glycerophospholipid metabolism takes place ubiquitously in mammalian tissues, and its defect causes an aberration of several tissue functions as well as abnormal lipid metabolism. Although this metabolic pathway has been known for over four decades, only recently the precise reactions and enzymes involved in this pathway have been revealed. This review will focus on the recent advances in our understanding of the sphingolipid metabolic pathway via S1P and its physiological and pathological roles. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.     

Molecular mechanisms of curcumins suppressing effects on tumorigenesis,angiogenesis and metastasis,focusing on NF-κB pathway

NF-κB pathway has long been considered as one of the potent prototypical pro-inflammatory signaling pathway and its role in several aspects of human health has been established. Recent studies have suggested that NF-κB activation is the master key in early development and pathobiology of several Cancers. Curcumin is a polyphenolic phytochemical compound with several stablished anti-inflammatory properties and is known to exert its anti-inflammatory effects mostly by interrupting NF-κB signaling pathway at multiple stages. Here we tried to provide a summary of recent finding, focusing on introducing NF-κB signaling pathways and its potential mechanism involved in development of several types of Cancers.     

The many faces of Notch signaling in skin-derived cells

Since the cloning of the Drosophila gene in the 1980s, decades of research have sought to dissect the intricacies of the mammalian Notch signaling cascade. The intrigue of this pathway undoubtedly lies in its ability to influence diverse cellular processes, including differentiation, cell fate, homeostasis, survival, proliferation and angiogenesis. Based on its evolutionary conservation and its fundamental role in development, it is not surprising that deregulation of the Notch signaling pathway can result in neoplastic growth. While originally of particular interest to immunologists based on its chief role in influencing T-cell fate decisions and tumor oncogenesis in T-cell acute lymphoblastic leukemia, pigment cell biologists have recently taken notice of the Notch cascade based on studies suggesting the importance of this pathway in regulating melanocyte stem cell survival and melanoma progression. We will review the Notch signaling literature as it relates to skin homeostasis, melanocytic stem cells and melanoma tumorigenesis.     

Therapeutic potential of targeting the Wnt/β-catenin pathway in the treatment of pancreatic cancer

The Wnt/β-catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β-catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.