苹果酸酶的分子生物学研究进展

苹果酸酶（malic enzyme,ME）是调控苹果酸代谢的关键酶,可以催化苹果酸氧化脱羧的可逆反应,产生丙酮酸和CO2,以及伴随NAD（P）^＋的还原反应。根据辅酶特异性,苹果酸酶可分为NAD^＋或NADP^＋依赖性苹果酸酶,并广泛存在于自然界中。苹果酸酶广泛地参与不同的代谢途径,包括C4植物中的固碳作用、真菌和动物中脂质合成的NADPH源泉、以及组织快速繁殖时线粒体能量的供给等。对苹果酸酶的生化特性、空间结构特点、催化机理的研究,将为代谢工程奠定基础。     

植物代谢工程研究进展

植物代谢工程是采用分子生物学、生物化学、功能基因组学、蛋白组学和代谢组学方法阐明植物复杂的代谢途径和代谢网络的分子机理,通过遗传工程技术在分子水平上调控代谢途径,以提高目标代谢物产量或降低有害代谢物的积累。本文综述了植物代谢工程,包括次生代谢关键酶基因工程、转录因子或调节基因的基因工程等方面的研究进展,以及系统生物学在植物代谢工程研究方面的应用。     

功能基因组学和代谢组学技术在植物次生代谢物合成及调控研究中的应用

植物次生代谢是植物在长期进化过程中与环境相互作用的结果,由初生代谢派生. 萜类、生物碱类、苯丙烷类为植物次生代谢物的主要类型,其代谢途径多以代谢频道形式存在,具有种属、生长发育期等特异性. 该文从植物次生代谢物的分类、代谢途径及代谢调控基因工程等方面展开论述,介绍了次生代谢物的生物合成途径,以及利用基因工程等技术对植物次生代谢途径进行遗传改良等方面的研究进展,为全面认识植物代谢网络、合理定位次生代谢及其关键酶、促进野生植物资源可持续利用等提供理论依据.      

Chemistry and world food supplies

Much of the unprecedented increase in developing countries' food production in the past two decades is due to chemical-based technologies and to the use of agricultural chemicals. However, these successes were won under generally favorable conditions of soil, climate, and irrigation water availability. The challenge of the future is to broaden the base of increased food production to include areas less well endowed with natural and economic resources. Chemistry and chemicals must play vital roles in this venture. Innovative chemical and biochemical approaches must be called upon to produce crop varieties, animal strains, and associated technologies to overcome constraints such as insects and diseases, acid and alkaline soils, and drought conditions. Genetic engineering will probably be a primary mechanism to achieve this goal.     

Metabolic interactions among environmental chemicals and drugs

It is evident that metabolic interactions can occur among drugs, insecticides, food additives, carcinogenic hydrocarbons, and a variety of environmental chemicals. A common denominator governing these effects is the versatile nature of the liver microsomal enzymes that metabolize chemicals with diverse structures and biological activities, and the fact that these enzymes can be stimulated or inhibited by other chemicals administered simultaneously. The discovery of these particular enzymes in the 1950's laid the groundwork for the current research on metabolic interactions. Such research provides information that is helpful in the evaluation of the safety and efficacy of drugs and environmental chemicals, and suggests new directions for further research. Some examples are as follows.     

微生物合成5-羟基色氨酸的研究进展

5?羟基色氨酸 (5-hydroxytryptophan，5-HTP)是血清素和褪黑素生物合成的中间代谢物，可有效治疗多种疾病，如抑郁症、头痛、肥胖和失眠等。传统生产5-HTP的方法是植物提取或化学合成，然而，这些方法效率低，难以大规模生产，无法满足不断增长的市场需求。随着代谢工程和合成生物学的发展，利用微生物合成目标产物成为必然趋势。笔者综述了微生物合成5-HTP的研究进展，通过定向进化羟化酶以及引入辅酶因子合成与再生途径，实现了微生物合成5-HTP，再经代谢工程调控，通过平衡宿主细胞内代谢流提高5-HTP生产效率，为工业微生物有效合成5-HTP提供了理论基础和技术支持。     

Frontiers in crop production: chemical research objectives

The science of chemistry and chemicals will continue to be an integral part of future crop production technologies. In assessing and defining the future role of chemistry three imperatives must be considered: (i) the necessity to preserve natural resources, (ii) the complementary solutions offered by the rapidly advancing biological sciences, and (iii) the specific requirements of developing regions where increasing crop productivity is most important. Chemical research objectives for improving crop protection and crop growth must take into account the perceivable and potential changes in crop production techniques, which, in turn, are dictated by a number of accentuating constraints.     

喜树碱生物合成途径及其相关酶研究现状及展望

喜树碱是从喜树Camptotheca acuminata中发现的单萜类吲哚生物碱,已经成为继紫杉醇之后广泛使用的植物性抗癌药,具有非常广阔的市场前景。研究喜树碱的生物合成途径,对于了解喜树碱的合成机制,提高次生代谢工程喜树碱的产量,解决目前资源紧缺造成的供求矛盾等问题均具有重要的意义。在查阅、综合文献的基础上,将喜树碱生物合成途径以异胡豆苷为分界线,分为上游途径和下游途径;并对各种中间产物合成、关键酶和关键基因等作了详细的阐述。在此基础上,提出了调控喜树碱合成的可能方法,并提出了喜树碱合成研究未来的研究重点。图3表1参29     

Redesigning metabolic routes: manipulation of TOL plasmid pathway for catabolism of alkylbenzoates

Increasing quantities of man-made organic chemicals are released each year into the biosphere. Some of these compounds are both toxic and relatively resistant to physical, chemical, or biological degradation, and they thus constitute an environmental burden of considerable magnitude. Genetic manipulation of microbial catabolic pathways offers a powerful means by which to accelerate evolution of biodegradative routes through which such compounds might be eliminated from the environment. In the experiments described here, a catabolic pathway for alkylbenzoates specified by the TOL plasmid of Pseudomonas was restructured to produce a pathway capable of processing a new substrate, 4-ethylbenzoate. Analysis of critical steps in the TOL pathway that prevent metabolism of 4-ethylbenzoate revealed that this compound fails to induce synthesis of the catabolic enzymes and that one of its metabolic intermediates inactivates catechol 2,3-dioxygenase (C23O), the enzyme that cleaves the aromatic ring. Consequently, the pathway was sequentially modified by recruitment of genes from mutant bacteria selected for their production of either an altered pathway operon regulator that is activated by 4-ethylbenzoate or an altered C23O that is less sensitive to metabolite inactivation. The redesigned pathway was stably expressed and enabled host bacteria to degrade 4-ethylbenzoate in addition to the normal substrates of the TOL pathway.     

药用植物基因组学研究进展

药用植物代表了最古老的药物形式,在许多国家的传统医学中使用数千年.药用植物是重要的自然资源,发展中国家高达80％的人口主要依赖植物来源的药物,全世界对草药的需求正在逐年递增,预计到2050年将达到5万亿美元,药用植物及其衍生物的大规模生产是不可避免的发展趋势.现代测序技术的飞速发展促进了药用植物基因组学的研究,基于基因组学的跨学科研究以及DNA和RNA、代谢组学和蛋白质组学的高通量数据分析,药用植物在代谢途径/酶、代谢物、基因、基因网络和蛋白质-蛋白质相互作用等研究领域取得突破.结合本团队相关研究工作对药用植物基因组学的最新研究进展进行综述,涉及利用结构基因组学和功能基因组学揭示各种药用植物的基因组序列信息、物种间进化、分子化合物动态变化以及药用成分合成等方面,这些数据为重要药材资源的分子辅助育种、基因组编辑以及对活性化合物化学多样性分子机制的理解提供了重要的理论基础.许多药材的植物化学成分和潜在的健康益处尚未得到研究或仍需要更深入地研究,药用植物的未来充满未知、希望,甚至惊喜.鉴于物种的多样性、环境因素的复杂性以及药用植物的全球分布,结合基因组学加强研究工作以开发新的和改良的药用植物品种势在必行.     

天然保鲜物料在食品保鲜上的应用研究

食品变质主要是由氧化和微生物作用引起的,目前使用的化学合成添加剂,其毒性和对人体的潜在危险,已引起严重关注,研究和开发天然的保鲜防腐物料已成为必然趋势,从辛香物料中提取保鲜组分,从茶叶中提取茶多酚,是目前最有希望的开发天然保鲜添加剂的途径,本文初步分析了食品的变质过程和天然保鲜组分的特性,并为这方面的深入研究提出了看法。     

Mining the biodiversity of plants: a revolution in the making

Only a small fraction of the immense diversity of plant metabolism has been explored for the production of new medicines and other products important to human well-being. The availability of inexpensive high-throughput sequencing is rapidly expanding the number of species that can be investigated for the speedy discovery of previously unknown enzymes and pathways. Exploitation of these resources is being carried out through interdisciplinary synthetic and chemical biology to engineer pathways in plant and microbial systems for improving the production of existing medicines and to create libraries of biologically active products that can be screened for new drug applications.     

热作废弃纤维资源利用与发展研究

我国热作废弃纤维资源丰富,其开发利用具有巨大的生态和经济价值。本文阐述近年来热作废弃纤维的综合利用现状,主要涉及饲料、肥料、功能性食品开发、制浆造纸、绿色化学品、生物质燃料开发、纳米纤维素等多个领域。对我国热作废弃纤维的资源化利用过程中存在的问题进行分析和讨论,并对其发展前景进行展望。     

Production of feedstock chemicals

Renewable raw materials may be converted by biological means to feedstocks for the chemical industry. Glucose from cornstarch is the current choice as a substrate, although advances may enable the use of less expensive lignocellulosic materals. The production of oxychemicals and their derivatives from renewable resources could amount to about 100 billion pounds annually, or about half of the U.S. production of organic chemicals. Ethanol produced by fermentation is now cost-competitive with industral ethanol produced from fossil fuel. Biological routes to other oxychemicals exist and are expected to be important in the future. Several product recovery methods may be used, but new energy-conserving methods will be needed to make the engineering-biology combinations economical.     

Biotechnology in the marine sciences

Genetic engineering applied to the production of fish, molluscs, algae, algal products, and crustaceans in natural environments and hatchery systems is still at the rudimentary stage. Cloning systems for producing commercially important chemicals, pharmacologically active compounds, and metamorphosis-stimulating substances present in marine organisms are being sought. Attempts are being made to develop useful drugs from the sea, including antineoplastic, antibiotic, growth-promoting (or -inhibiting), analgesic, and antispasmodic agents. Immediate commercial applications can be expected from engineered systems involving polysaccharide and specialty chemical production, with marine microorganisms as the source of genetic material.     

产乙醇重组大肠杆菌的研究进展

利用微生物从低廉的纤维素、半纤维素及其水解产物生产生物燃料乙醇受到高度重视。代谢工程技术构建和改造高产乙醇重组菌成为研究的重点。着重概述了产乙醇重组大肠杆菌的研究进展。以大肠杆菌作为模式菌株进行乙醇代谢工程改造的研究和探索,将为新型的产乙醇重组微生物提供技术依据和借鉴。     

Achieving diversity in the face of constraints: lessons from metabolism

Metabolic engineering of plants can reduce the cost and environmental impact of agriculture while providing for the needs of a growing population. Although our understanding of plant metabolism continues to increase at a rapid pace, relatively few plant metabolic engineering projects with commercial potential have emerged, in part because of a lack of principles for the rational manipulation of plant phenotype. One underexplored approach to identifying such design principles derives from analysis of the dominant constraints on plant fitness, and the evolutionary innovations in response to those constraints, that gave rise to the enormous diversity of natural plant metabolic pathways.     

Network rigidity and metabolic engineering in metabolite overproduction

In order to enhance the yield and productivity of metabolite production, researchers have focused almost exclusively on enzyme amplification or other modifications of the product pathway. However, overproduction of many metabolites requires significant redirection of flux distributions in the primary metabolism, which may not readily occur following product deregulation because metabolic pathways have evolved to exhibit control architectures that resist flux alterations at branch points. This problem can be addressed through the use of some general concepts of metabolic rigidity, which include a means for identifying and removing rigid branch points within an experimental framework.     

微生物发酵法生产2,3-丁二醇瓶颈因素分析

2,3-丁二醇（2,3-Butanediol）是一种极具价值的化工原料和液体燃料,应用广泛。许多微生物都能代谢产生2,3-丁二醇,但产率有差异。本文着重从发酵菌株、代谢途径、发酵底物、发酵工艺以及分离提取方法等方面概述了微生物发酵法生产2,3-丁二醇的研究进展,并讨论了2,3-丁二醇发酵过程中存在的问题和瓶颈因素。指出应从选育理想菌株出发,并对2,3-丁二醇的生化代谢途径中不同酶的动力学进行针对性的研究,以廉价的发酵底物及高效节能的分离纯化工艺进行发酵工艺优化,在此基础上进一步对2,3-丁二醇的系列衍生物进行开发应用,以降低生产成本,提高2,3-丁二醇的产量。     

Natural plant chemicals: sources of industrial and medicinal materials

Many higher plants produce economically important organic compounds such as oils, resins, tannins, natural rubber, gums, waxes, dyes, flavors and fragrances, pharmaceuticals, and pesticides. However, most species of higher plants have never been described, much less surveyed for chemical or biologically active constituents, and new sources of commercially valuable materials remain to be discovered. Advances in biotechnology, particularly methods for culturing plant cells and tissues, should provide new means for the commercial processing of even rare plants and the chemicals they produce. These new technologies will extend and enhance the usefulness of plants as renewable resources of valuable chemicals. In the future, biologically active plant-derived chemicals can be expected to play an increasingly significant role in the commercial development of new products for regulating plant growth and for insect and weed control.