How Organisms Adapt to New Enzymes and Pathways

细菌和其他生物生活在一个不断变化的，通常是敌对的环境中。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环境。例如，这些新的活动可能使它们能够破坏一种新的抗生素或解毒一种环境污染物，或者可能使它们能够利用同样的污染物作为营养来源，大胆地在以前没有微生物生长的地方生长。这些新的活动也可能突然使无害的微生物变成致命的人类病原体。达尔文预测了生物体表型多样性产生的所有主要机制，除了一个：遗传信息从一个生物体到另一个生物体的水平转移，导致立即获得新的酶，或者在某些情况下，一个全新的代谢途径。随着完整基因组序列的出现，现在很清楚，细菌中至少四分之一，有时更多的基因可能是通过这种方式从外部获得的。这一自然过程也模仿了科学家在实验室中试图设计微生物以产生有用物质或降解环境毒素的过程。然而，对于生物体如何对一种或一组新酶的引入作出反应，以及它们随后如何修改新基因和自己的基因，以产生具有新特性的新物种，人们知之甚少。该项目的总体目标是建立一个模型系统，用于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-以及被-生物体中已经存在的核心途径所影响。为了解决这个基本的生物学问题，一个具有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）专业知识的团队已经组建起来，并选择了一个模型系统。该项目将把曼德拉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，并跟踪它们的进化，使其适应以内酰胺为碳源生长。了解细胞如何对新的酶和途径作出反应对生物学非常重要，因为这一过程是细胞水平进化基本机制的关键部分。该项目将提供有关生物体如何适应和进化的新的基本信息。它还将提供指导方针，以便更有效地将新活动植入细菌，用于工业和环境用途。这个项目的跨学科性质意味着具有广泛背景的人可以贡献并从结果中受益。该项目还为中学教师、少数民族学生和非博士学生提供了机会。-授予机构探索广泛的基本问题和学习广泛的技术。我们打算以各种形式广泛地提供结果，从中学教育到高级应用研究项目都可以使用这些结果。

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.