Enabling synthetic biology through single cell functional genomics

项目摘要。在复杂的生态系统中，微生物利用次生代谢作为交流的手段 并控制当地的环境。其中一些产品对治疗有着深远的效用 人类疾病，特别是传染病，目前处方的抗生素中有很大一部分 基于或衍生自微生物来源的天然产物。该计划开发，评估和 实施了一种新的基于活性的单细胞基因组学方法，用于发现来自 宿主相关的海洋微生物该合作项目的研究包括样本收集、单个 细胞基因组学，基因组数据的生物信息学分析，重点是抗生素产生基因簇， 将最有希望的簇工程化到宿主菌株中，并基于流式细胞术指导这些簇的生产。 化合物.以三种海洋软体大型生物（裸鳃类、被囊类和 海绵），我们的团队将使用一种新的酶选择的方法来确定未开发的PKS生产共生体 微生物，为PKS系统评估它们的基因组，并使用这些基因组数据来指导 实验室易处理宿主中的PKS生产。预期的结果将促进新的发现 从海洋动物的微生物组中提取抗生素候选物。

Project Summary. In complex ecosystems, microbes use secondary metabolism as a means to communicate within and control their local environment. Some of these products have had profound utility for the treatment of human diseases, particularly infectious disease, where a large percentage of currently prescribed antibiotics are based on or derived from natural products of microbial origin. This program develops, evaluates and implements a new activity-based single cell genomics approach for the discovery of antibiotic candidates from host-associated marine microbes. The research in this collaborative program involves sample collection, single cell genomics, bioinformatics analysis of genomic data with focus on antibiotic producing gene clusters, engineering the most promising clusters into host strains, and flow cytometry-based guided production of these compounds. Using three marine soft-bodied macroorgansims as models (nudibranchs, tunicates and sponges), our team will use a new synthase-selected approach to identify unexplored PKS producing symbiotic microbes, evaluate their genomes for PKS systems and use this genomic data to guide the reconstruction of PKS production in laboratory tractable hosts. The expected results will advance the discovery of novel antibiotic candidates from the microbiomes of marine animals.