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

许多药物是由微生物产生的，用于治疗人类和动物的疾病。对许多此类药物来说，制造成本是一个严重的问题。一个主要的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整体生产成本。一种微生物是光合作用微生物。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。这样就不需要购买昂贵的营养物质，从而降低了药物制造的成本。在这个项目中，目标产品将是内溶素，这是一种对抗鸡感染的新型治疗方法，可以潜在地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阶段的学生进行共同文化教育，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过程的主要成本。在自然界中，丝状真菌是地衣的一部分，地衣是光合自养生物（光生物）与其伴侣（通常是类似曲霉的真菌）之间的共生。光生物提供有机碳，利用二氧化碳和阳光产生，以配合真菌物种。真菌产生有用的生物化学物质。该项目的目标是实现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。将确定允许曲霉和蓝藻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基因组规模的共培养模型来表征，该模型包含转录组学、蛋白质组学和代谢数据。该模型将用于确定培养基组成和培养制度，以优化我们的合成地衣的生长和生产能力。然后，合成的地衣将产生一种新的抗微生物肽，内毒素，它可以取代抗生素治疗鸡的细菌感染。总的来说，该项目将开发一个低成本的平台，用于生产各种治疗分子和蛋白质。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.