Investigating Unsequenced Enzymatic Activities: A Preliminary to Enzyme Genomics

研究未测序的酶活性：酶基因组学的初步研究

• 批准号: 0438571
• 负责人: Peter Karp
• 金额: $ 7.85万
• 依托单位: SRI International
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0438571&HistoricalAwards=false
• 关键词: Investigating; Unsequenced; Enzymatic; Activities; Preliminary

An analysis of the contents of the ENZYME database has revealed that prima facia, no gene or protein sequence is known for more than 1400 enzyme activities, corresponding to 38% of enzyme classification (EC) numbers. This lack of sequence data for such a large fraction of enzyme activities hinders research and biotechnology in a number of areas ranging from genome annotation to metabolic engineering and pathway prediction. Fortunately, the recent availability of large numbers of completely sequenced genomes enables the eventual identification of the genes encoding these enzymes using data available in the literature, combined with computational and experimental analyses. The overall goals of the project are to perform a survey of the literature associated with orphan activities to further substantiate that their existence is not artifactual, and to capture data from this literature, which would facilitate the identification of the genes encoding these activities. Thus, the project will 1) authenticate orphan activities; 2) capture and disseminate data that could enable the identification of the genes coding for enzymes associated with orphan activities; and 3) submit any sequence data found in the literature to the UniProt database. The survey will be applied to a randomly selected subset of orphan activities large enough to provide reasonably solid conclusions relative to the universe of orphan activities.Intellectual MeritsAssessment of the authenticity of orphan activities: Determining an upper bound on the rate of artifactual causes for orphan activities will inform the decision as to whether to proceed with an Enzyme Genomics Initiative. Similarly, extracting molecular properties and other data from the literature associated with orphan activities will help determine the extent to which such an Initiative is warranted.Enhanced genome annotation: The availability of gene and protein sequences encoding previously orphan activities will enhance our ability to annotate genomes in terms of both coverage (fraction of genes that can be recognized), and accuracy (fraction of predicted gene functions that are correct).Enhanced pathway prediction: The availability of sequence data from previously orphaned activities will also increase our ability to predict computationally the metabolic pathway component of organisms, since such predictions typically rely upon sequence data from known enzymatic activities.Enhanced metabolic engineering: These sequence data will also enhance the practice of metabolic engineering, again because of its dependency upon sequences from known enzymatic activities.Broader ImpactsIncreased database accuracy: The outcome of this work will result in the expansion of enzyme sequences in the UniProt Database, a major protein information database.Increased value of existing data: The results of this work will add value to a large body of enzymology whose full value is not realized currently because of the absence of sequence data, and will further leverage systematic genome sequencing.

对酶数据库内容的分析显示，表面上，已知的基因或蛋白质序列没有超过1400个酶活性，对应于38%的酶分类（EC）编号。缺乏如此大一部分酶活性的序列数据阻碍了从基因组注释到代谢工程和途径预测等许多领域的研究和生物技术。幸运的是，最近大量完全测序的基因组的可用性使得最终识别编码这些酶的基因能够使用文献中可用的数据，并结合计算和实验分析。该项目的总体目标是对与孤儿活动相关的文献进行调查，以进一步证实它们的存在不是人为的，并从这些文献中获取数据，这将有助于识别编码这些活动的基因。因此，该项目将1)鉴定孤儿活动；2)获取和传播能够鉴定与孤儿病活性相关的酶的编码基因的数据；3)将文献中找到的任何序列数据提交到UniProt数据库。该调查将应用于随机选择的孤儿活动子集，其规模足以提供相对于孤儿活动范围的合理可靠的结论。孤儿活动真实性的智力价值评估：确定孤儿活动人为原因率的上限，将为是否继续进行酶基因组学计划的决定提供信息。同样，从与孤儿活动相关的文献中提取分子特性和其他数据将有助于确定此类倡议的保证程度。增强的基因组注释：编码先前孤儿活动的基因和蛋白质序列的可用性将增强我们在覆盖率（可识别的基因比例）和准确性（预测的基因功能的正确比例）方面对基因组进行注释的能力。增强的途径预测：从先前孤立的活动中获得的序列数据的可用性也将提高我们计算预测生物体代谢途径成分的能力，因为这种预测通常依赖于已知酶活性的序列数据。增强的代谢工程：这些序列数据也将增强代谢工程的实践，因为它依赖于已知酶活性的序列。更广泛的影响提高数据库的准确性：这项工作的结果将导致UniProt数据库（一个主要的蛋白质信息数据库）中酶序列的扩展。增加现有数据的价值：这项工作的结果将为大量的酶学增加价值，这些酶学的全部价值目前由于缺乏序列数据而无法实现，并将进一步利用系统的基因组测序。