The making of the minibody: An engineered β-protein for the display of conformationally constrained peptides

Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue β-protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage.     

Reflections on biosystems motivating supramolecular engineering

Some goals of bioelectronics—interfacing biology and electronics — are the understanding of supramolecular bioprocesses and the construction of supramolecular devices. The principles for the design and fabrication of machineries with functional components of molecular size are inspired by reflecting on biosystems, and it seems important to consider such principles. We first discuss attempts to construct supramolecular machines, and then we consider the bacterial reaction centre as an example where supramolecular engineering helps to elucidate a bioprocess. We then discuss possible mechanisms leading to the emergence of life-like systems in the light of the basic principles used to design supramolecular devices. Finally, we reflect on prospects in molecular engineering inspired by studying the emergence of life-like systems.     

Metabolic engineering of plant secondary products

Plants interact with their environment by producing a diverse array of secondary metabolites. Many of these compounds are valued for their medicinal, industrial or agricultural properties. Other secondary products are toxic or otherwise undesirable and can reduce the commercial value of crops. Gene transfer technology offers new opportunities to modify directly plant secondary product synthesis through metabolic engineering. This article reviews some of the strategies which have been used to increase or decrease the synthesis of specific plant metabolites, as well as methods for expanding the biosynthetic capabilities of individual species.     

四种鹭类繁殖生态生物学研究

本文对夜鹭,白鹭,黄鹭白鹭,池鹭混群在同一巢区的繁殖,种间协高及雏鸟生长进行进行了观察研究,其中黄嘴白路豫南大别山类新纪录,在此繁殖亦为首次发现。几种路在巢位,食性,取食活动和习性方面都表现出其混居同一巢地繁殖的种间协调性,符合高期假说。比较４种鹭鸟雏鸟生长过程中各生长参数。其中池鹭虽个体最小,但体重和各部位生长却对较快。     

不同生境下蓝桉的木材解剖研究

用光镜及扫描电镜对不同生境下的蓝桉（Ｅｕｃａｌｙｐｔｕｓｇｌｏｂｕｌｕｓ Ｌａｂｉｌｌ．）木材结构进行了解剖学观察,描述了木材结构特征。以蓝桉木材的１１ 个主要特征——导管频率、单孔率、导管直径、导管分子长度、管胞长度和直径、纤维管胞长度和直径、纤维长度、射线频率和高度为指标,对生长在不同生境下的蓝桉进行比较发现：随着纬度的增加,生长轮变化不明显;木材中大部分组成分子的数量特征,除导管频率有降低趋势外均与纬度成正相关。评述了年降雨量对蓝桉木材结构的影响     

新型双分子细胞因子融合蛋白研究进展

细胞因子通过相互协调、相互制约在体内发挥着重要的免疫调节作用,利用细胞因子的这一特点,近年来国内外设计并构建了新型的第二代细胞因子,即利用基因工程技术和蛋白质工程技术将两种细胞因子合二为一,使之成为具有多功能的嵌合蛋白新品种,为细胞因子的理论研究及临床应用提供了新的手段与方法.     

合理用药生态控制茶小绿叶蝉主要措施与评价

合理用药生态控制茶小绿叶蝉主要措施与评价张觉晚,王沅江（湖南省茶叶研究所,长沙４１０１４５）ＰｒｉｎｃｉｐａｌＴｅｃｈｎｉｑｕｅｓｏｆＲａｔｉｏｎａｌＵｓｅｏｆＰｅｓｔｉｃｉｄｅｆｏｒＥｃｏｌｏｇｉｃａｌＣｏｎｔｒｏｌｏｖｅｒＴｅａＧｒｅｓｎＬｅａｆ...     

城市生态园林与生物多样性保护

城市生态园林与生物多样性保护袁兴中,刘红（曲阜师范大学,２７３１６５）ＵｒｂａｎＥｃｏｌｏｇｉｃａｌｇａｒｄｅｎｉｎｇａｎｄＢｉｏｄｉｖｅｒｓｉｔｙＣｏｎｓｅｒｖａｔｉｏｎ．￥ＹｕａｎＸｉｎｇｚｈｏｎｇ;ＬｉｕＨｏｎｇ（Ｄｅ－ｐａｒｔｍｅｎｔｏｆＢｉ...     

Metabolic engineering of Clostridium acetobutylicum ATCC 824 for increased solvent production by enhancement of acetone formation enzyme activities using a synthetic acetone operon

The ability to genetically alter the product-formation capabilities of Clostridium acetobutylicum is necessary for continued progress toward industrial production of the solvents butanol and acetone by fermentation. Batch fermentations at pH 4.5, 5.5, or 6.5 were conducted using C. acetobutylicum ATCC 824 (pFNK6). Plasmid pFNK6 contains a synthetic operon (the "ace operon") in which the three homologous acetone-formation genas (adc, ctfA, and ctfB) are transcribed from the adc promoter. The corresponding enzymes (acetoacetate decarboxylase and CoA-transferase) were best expressed in pH 4.5 fermentations. However, the highest levels of solvents were attained at pH 5.5. Relative to the plasmid-free control strain at pH 5.5, ATCC 824 (pFNK6) produced 95%, 37%, and 90% higher final concentrations of acetone, butanol, and ethanol, respectively; a 50% higher yield (g/g) of solvents on glucose; and a 22-fold lower mass of residual carboxylic acids. At all pH values, the acetone-formation enzymes were expressed earlier with ATCC 824 (pFNK6) than in control fermentations, leading to earlier induction of acetone formation. Furthermore, strain ATCC 824 (pFNK6) produced butanol significantly earlier in the fermentation and produced significant levels of solvents at pH 6.5. Only trace levels of solvents were produced by strain ATCC 824 at pH 6.5. Compared with ATCC 824, a plasmid-control strain containing a vector without the ace operon also produced higher levels of solvents [although lower than those of strain ATCC 824 (pFNK6)] and lower levels of acids. Strains containing plasmid-borne derivatives of the ace operon, in which either the acetoacetate decarboxylase or CoA-transferase alone were expressed at elevated levels, produced acids and solvents at levels similar to those of the plasmid-control strain. (c) 1993 John Wiley & Sons, Inc.