CAREER: Genetic and Functional Characterization of Microbial Secondary Lipid Biosynthesis - a Biomes to Biotechnology Investigation

知识价值。微生物合成脂肪酸衍生烃分子（烷烃和烯烃）作为可再生燃料和化学品的潜在来源，近年来引起了人们的强烈兴趣。要实现这一潜力，就必须从分子水平上了解微生物碳氢化合物生物合成过程中涉及的基因和基因功能，以及它们与脂肪酸生物合成过程的关系，脂肪酸生物合成过程为这些碳氢化合物产品提供了化学主干。目前的项目重点研究了几种新发现的微生物生物合成途径，这些途径催化形成次级脂质和辅助脂质分子，这些脂质分子在化学上与核心（初级）脂肪酸产物不同，并通过不同微生物谱系的新型生物合成机制合成。我们目前对与次生脂质生物合成途径相关的化学产品的了解严重有限。同样，这些脂类的生物学功能也是未知的。本CAREER项目的目标是表征独特的微生物脂肪酸和脂肪酸衍生烃生物合成的遗传和生理基础。这项研究的一个关键成果将是一个转化框架，将涉及脂质和碳氢化合物合成的功能多样的微生物过程与脂质多样化的生理、生态和进化基础结合起来。为了应对这些突出的科学问题并推进可再生商品碳氢化合物生产的科学基础，研究策略涉及三个协同的具体目标：途径发现、产品发现和生理意义。通过整合综合数据挖掘策略，利用所有可用的基因组和宏基因组序列档案，以及对脂质和碳氢化合物生物合成活动的环境样本的直接询问，拟议的研究将为微生物脂质代谢提供重要的新见解，因为它与生物能源应用有关。更广泛的影响。除了对生物能源的科学和社会影响外，该项目还将直接有助于生物信息学、遗传学、分析化学和生物技术等不同科学学科的教学和培训。为了加强研究和教育的基础设施，这项研究的一个关键成果将是一个致力于微生物脂质和碳氢化合物生物合成的综合数据库。这一研究部分将为潜在的生物技术应用和开发提供可操作的数据。此外，为了扩大这项研究的影响并吸引更广泛的学生，将开发一个全球可访问的教育资源，突出生物发现到生物技术应用的令人兴奋的概念。交互式学习和分析门户网站将作为一般生物学，基因组学和计算生物学教育平台，并将作为高级微生物生态学研究和分析（CAMERA）资源的社区网络基础设施的一部分整合。

Intellectual Merit. Microbial synthesis of fatty-acid-derived hydrocarbon molecules (alkanes and alkenes) has garnered intense interest in recent years as potential sources of renewable fuels and chemicals. Realization of this potential necessitates a molecular-level understanding of the genes and gene functions involved in microbial hydrocarbon biosynthesis and their relationship with the fatty acid biosynthetic processes that provide the chemical backbone for these hydrocarbon products. The current project focuses on several newly discovered microbial biosynthetic pathways catalyzing the formation of secondary lipids, accessory lipid molecules that are chemically distinct from core (primary) fatty acid products and synthesized via a novel biosynthetic mechanism in diverse microbial lineages. Our current knowledge of chemical products associated with secondary lipid biosynthetic pathways is severely limited. Likewise, the biological function(s) of these lipid classes is unknown. The goal of this CAREER project is to characterize the genetic and physiological basis of unique microbial fatty acid and fatty acid-derived hydrocarbon biosynthesis. A key deliverable of this research will be a translational framework uniting functionally diverse microbial processes involved in lipid and hydrocarbon synthesis with the physiological, ecological and evolutionary underpinnings of lipid diversification. To confront these outstanding scientific questions and advance the scientific foundation for the production of renewable commodity hydrocarbons, the research strategy involves three synergistic specific aims: Pathway Discovery, Product Discovery, and Physiological Significance. By integrating comprehensive data-mining strategies that leverage all available genomic and metagenomic sequence archives and the direct interrogation of environmental samples for lipid and hydrocarbon biosynthetic activities, the proposed research will deliver important new insight into microbial lipid metabolism as it relates to bioenergy applications.Broader Impacts. In addition to its scientific and societal impacts relevant to bioenergy, this project will directly contribute to the teaching and training of students in diverse scientific disciplines including bioinformatics, genetics, analytical chemistry, and biotechnology. To enhance the infrastructure for research and education, one key deliverable of this research will be a comprehensive database devoted to microbial lipid and hydrocarbon biosynthesis. This research component will provide actionable data for potential biotechnological application and exploitation. Furthermore, to extend the impact of this research and engage a broader student audience, a globally accessible educational resource will be developed highlighting the exciting concept of biological discovery to biotechnological application. The interactive learning and analysis portal will serve as a general biology, genomics and computational biology educational platform and will be integrated as part of the Community cyberinfrastructure for Advanced Microbial Ecology Research and Analysis (CAMERA) resource.