How Organisms Adapt to New Enzymes and Pathways

生物体如何适应新的酶和途径

• 批准号: 0425719
• 负责人: Gregory Petsko
• 金额: --
• 依托单位: Brandeis University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0425719&HistoricalAwards=false
• 关键词: How; Organisms; Adapt; New; Enzymes

Bacteria and other organisms live in a constantly changing, often hostile environment. To survive, they must adapt by developing new enzymes and new metabolic processes. These new activities might, for example, enable them to destroy a new antibiotic or detoxify an environmental pollutant, or might enable them to use that same pollutant as a source of nutrients, to boldly grow where no microbe has grown before. The new activities may also suddenly cause a harmless microbe to become a deadly human pathogen. Darwin anticipated all of the major mechanisms for the generation of phenotypic diversity in living organisms except one: the horizontal transfer of genetic information from one organism to other, resulting in the immediate acquisition of a new enzyme or, in some cases, an entire new metabolic pathway. With the advent of complete genome sequences, it is now clear that at least a quarter, sometimes more, of the genes in a bacterium have probably been acquired from outside in this way. This natural process also mimics what scientists do in the lab when they try to engineer microbes to produce useful substances or degrade environmental toxins. Yet little is known about how organisms respond to the introduction of a new enzyme or set of enzymes and how they subsequently modify both the new genes and their own to generate a new species with new properties. The overall aim of this project is to develop a model system for studying the origin, control and integration of new enzymes and new metabolic pathways, and to utilize this system to discover the factors that govern their evolution; to develop new ways of modeling them effectively; and to understand how their presence influences - and is influenced by - the core pathways already present in the organism. To address this fundamental biological question, a team with expertise in microbial genetics and physiology, mechanistic enzymology, molecular biology, structural biology, and systems biology, including bioinformatics, has been assembled, and a model system has been chosen. The project will transfer the enzymes of the mandelamide pathway from the soil bacterium Pseudomonas putida into E. coli, and follow their evolution as the organism adapts to use them to grow on lactamide as a carbon source. Understanding how a cell responds to new enzymes and pathways is of great importance to biology because this process is a key part of the fundamental machinery of evolution at the cellular level. The project will yield new basic information about how organisms adapt and evolve. It will also provide guidelines for the more effective engineering of new activities into bacteria for industrial and environmental uses. The interdisciplinary nature of this project means that people with a wide range of backgrounds can contribute and can benefit from the results. The project also provides opportunities for secondary school teachers and students from minority and non-Ph.D.-granting institutions to explore a wide range of basic questions and to learn a broad range of techniques. We intend to make the results widely available in a variety of forms that can be used from secondary education through to advanced applied research projects.

细菌和其他生物体生活在不断变化且往往充满敌意的环境中。 为了生存，它们必须通过开发新的酶和新的代谢过程来适应。例如，这些新活动可能使它们能够破坏新的抗生素或对环境污染物进行解毒，或者可能使它们能够使用相同的污染物作为营养源，在以前没有微生物生长的地方大胆地生长。 新的活动也可能突然导致无害的微生物变成致命的人类病原体。 达尔文预见到了生物体中产生表型多样性的所有主要机制，除了一个：遗传信息从一种生物体水平转移到另一种生物体，导致立即获得一种新的酶，或者在某些情况下，形成一种全新的代谢途径。 随着完整基因组序列的出现，现在已经清楚，细菌中至少四分之一，有时甚至更多的基因可能是通过这种方式从外部获得的。 这种自然过程也模仿了科学家在实验室中尝试改造微生物来生产有用物质或降解环境毒素时所做的事情。 然而，人们对生物体如何响应一种新酶或一组酶的引入以及它们随后如何修改新基因及其自身基因以产生具有新特性的新物种知之甚少。 该项目的总体目标是开发一个模型系统来研究新酶和新代谢途径的起源、控制和整合，并利用该系统发现控制其进化的因素；开发有效建模的新方法；并了解它们的存在如何影响生物体中已经存在的核心途径，以及如何受其影响。 为了解决这个基本的生物学问题，我们组建了一支在微生物遗传学和生理学、机械酶学、分子生物学、结构生物学和系统生物学（包括生物信息学）方面具有专业知识的团队，并选择了一个模型系统。 该项目将把扁桃酰胺途径的酶从土壤细菌恶臭假单胞菌转移到大肠杆菌中，并随着有机体适应使用它们以乳酰胺作为碳源生长而跟踪它们的进化。 了解细胞如何响应新的酶和途径对于生物学非常重要，因为这个过程是细胞水平进化基本机制的关键部分。 该项目将产生有关生物体如何适应和进化的新的基本信息。 它还将为更有效地将新活性工程转化为工业和环境用途的细菌提供指导。 该项目的跨学科性质意味着具有广泛背景的人们可以做出贡献并可以从结果中受益。 该项目还为来自少数民族和非博士学位授予机构的中学教师和学生提供了探索广泛的基本问题和学习广泛的技术的机会。 我们打算以各种形式广泛提供研究成果，从中等教育到高级应用研究项目。