Collaborative Research: Synthetic Lichen Co-Cultures for Sustainable Generation of Biotechnology Products

合作研究：用于可持续生成生物技术产品的合成地衣共培养物

• 批准号: 1804733
• 负责人: Michael Betenbaugh
• 金额: $ 27.9万
• 依托单位: Johns Hopkins University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1804733&HistoricalAwards=false
• 关键词: Collaborative; Research; Synthetic; Lichen; Co

Many drugs are produced by microbes and used to treat diseases in humans and animals. The cost of manufacturing is a serious issue for many of these drugs. One major cost is for the nutrients required by these microbes to grow and produce the drug. The goal of this project is to lower nutrient costs and overall production costs by growing two microbes together. One microbe is photosynthetic. It will utilize sunlight and carbon dioxide to generate nutrients that are then consumed by the other microbe. This removes the need to purchase expensive nutrients, decreasing the cost of drug manufacture. In this project, the target product will be endolysin, a novel treatment against chicken infections that can potentially avoid the widespread use of antibiotics in the poultry industry. The project will also educate students from the high school to the graduate level about co-cultures, preparing them for employment in the growing biomanufacturing industry.Commercially, filamentous fungi like Aspergillus produce enzymes, antibiotics, and metabolites. Economic analysis reveals that the cost of organic carbon feedstocks is a major cost for these processes. In nature, filamentous fungi are found as part of lichens, which are a symbiosis between a photosynthetic autotroph (photobiont) and its partner, typically a fungus similar to Aspergillus. The photobiont provides organic carbon, generated using carbon dioxide and sunlight, to partner fungal species. The fungi generate useful biochemicals. The goal of this project is to implement synthetic lichen co-cultures as a transformative biomanufacturing platform for the production of a novel antimicrobial peptide. Cultivation conditions that allow Aspergillus and cyanobacteria to grow successfully together will be identified. Interactions between the two partners will be characterized using genome scale co-culture models that incorporate transcriptomics, proteomics, and metabolic data. This model will be used to determine the media composition and cultivation regime that optimizes the growth and production capabilities of our synthetic lichen. The synthetic lichen will then generate a novel anti-microbial peptide, endolysin, which could replace antibiotics for the treatment of bacterial infections in chickens. Overall, the project will develop a low-cost platform for the production of a wide variety of therapeutic molecules and proteins.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

许多药物是由微生物生产的，用于治疗人类和动物的疾病。对于许多此类药物来说，生产成本是一个严重的问题。其中一项主要成本是这些微生物生长和生产药物所需的营养物质。该项目的目标是通过同时培养两种微生物来降低营养成本和总体生产成本。一种微生物可以进行光合作用。它将利用阳光和二氧化碳产生营养物质，然后被其他微生物消耗。这样就无需购买昂贵的营养素，从而降低了药品生产成本。在该项目中，目标产品将是细胞内溶素，这是一种针对鸡感染的新型治疗方法，有可能避免在家禽业中广泛使用抗生素。该项目还将对从高中到研究生的学生进行共培养方面的教育，为他们在不断发展的生物制造行业就业做好准备。商业上，像曲霉这样的丝状真菌会产生酶、抗生素和代谢物。经济分析表明，有机碳原料的成本是这些工艺的主要成本。在自然界中，丝状真菌是地衣的一部分，是光合自养生物（光生物体）与其伙伴（通常是类似于曲霉属的真菌）之间的共生体。 光生物提供利用二氧化碳和阳光产生的有机碳来与真菌物种合作。真菌产生有用的生化物质。 该项目的目标是实施合成地衣共培养作为生产新型抗菌肽的变革性生物制造平台。将确定允许曲霉属和蓝藻菌一起成功生长的培养条件。两个合作伙伴之间的相互作用将使用包含转录组学、蛋白质组学和代谢数据的基因组规模共培养模型来表征。该模型将用于确定优化我们的合成地衣的生长和生产能力的培养基成分和栽培方式。 然后，合成地衣将产生一种新型抗微生物肽——细胞内溶素，它可以替代抗生素来治疗鸡的细菌感染。总体而言，该项目将开发一个低成本平台，用于生产各种治疗分子和蛋白质。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Dynamic resource allocation drives growth under nitrogen starvation in eukaryotes

• DOI: 10.1038/s41540-020-0135-y
• 发表时间: 2020-05
• 期刊: npj Systems Biology and Applications
• 影响因子: 4
• 作者: Juan D. Tibocha-Bonilla;Manish Kumar;Anne Richelle;R. Godoy-Silva;K. Zengler;C. Zuñiga

Modeling of nitrogen fixation and polymer production in the heterotrophic diazotroph Azotobacter vinelandii DJ

异养固氮菌 Azotobacter vinelandii DJ 的固氮和聚合物生产模型

• DOI: 10.1016/j.mec.2020.e00132
• 发表时间: 2020
• 期刊: Metabolic Engineering Communications
• 影响因子: 5.2
• 作者: Tec-Campos, Diego;Zuñiga, Cristal;Passi, Anurag;Del Toro, John;Tibocha-Bonilla, Juan D.;Zepeda, Alejandro;Betenbaugh, Michael J.;Zengler, Karsten
• 通讯作者: Zengler, Karsten

A Novel Sparse Compositional Technique Reveals Microbial Perturbations

• DOI: 10.1128/msystems.00016-19
• 发表时间: 2019-01-01
• 期刊: MSYSTEMS
• 影响因子: 6.4
• 作者: Martino, Cameron;Morton, James T.;Zengler, Karsten
• 通讯作者: Zengler, Karsten

Synthetic microbial communities of heterotrophs and phototrophs facilitate sustainable growth

• DOI: 10.1038/s41467-020-17612-8
• 发表时间: 2020-07
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: C. Zuñiga;Tingting Li;M. Guarnieri;J. Jenkins;Chien-Ting Li;Kerem Bingol;Young-Mo Kim;M. Betenbaugh-M.-Be

Creating a synthetic lichen: Mutualistic co-culture of fungi and extracellular polysaccharide-secreting cyanobacterium Nostoc PCC 7413

• DOI: 10.1016/j.algal.2019.101755
• 发表时间: 2020-01-01
• 期刊: ALGAL RESEARCH-BIOMASS BIOFUELS AND BIOPRODUCTS
• 影响因子: 5.1
• 作者: Li, Tingting;Jiang, Liqun;Betenbaugh, Michael J.
• 通讯作者: Betenbaugh, Michael J.