CAREER: A Red Yeast Cell Factory

职业：红酵母细胞工厂

• 批准号: 1944046
• 负责人: Eric Young
• 金额: $ 51.26万
• 依托单位: Worcester Polytechnic Institute
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1944046&HistoricalAwards=false
• 关键词: CAREER; Red; Yeast; Cell; Factory

Different types of microorganisms have been found that produce chemical compounds and function at activity levels that have not been seen previously. New genetic tools must be developed in order to exploit their abilities fully. This research project focuses on developing such tools for a specific type of yeast named Xanthophyllomyces dendrorhous, often referred to as red yeast. This organism was chosen for study due its ability to produce astaxanthin, an antioxidant related to beta-carotene. Astaxanthin has exhibited some success in treating many diseases, including Alzheimer’s, Parkinson’s, high cholesterol, and diabetes. Harnessing red yeast's ability to make this molecule will enable the production of a large number of related compounds that potentially have a broad range of uses. Graduate students involved in this project will be trained through course development, laboratory research, and continuing education programs. These efforts will prepare the next generation of engineers as the rapid pace of synthetic biology innovation continues to transform biomanufacturing.This research project involves using genomics approaches to understand and engineer a basidiomycete yeast, Xanthophyllomyces dendrorhous, often referred to as red yeast. Red yeast is genetically tractable, generally regarded as safe, and used to manufacture the terpenoid astaxanthin. This organism has promise as a terpenoid production platform because it produces precursor pools for nearly all terpenoids. A major aim of this research is to create a terpenoid cell factory for several different valuable compounds using red yeast as a host. Transcriptomics will be used to study the genetic basis of unique gene regulation and photobiology. The goal is to harness these unique traits using a high-throughput combinatorial strain engineering approach. This process will modify the host and heterologous pathway simultaneously to improve terpenoid titer and productivity. Along the way, the project will advance basidiomycete engineering strategies and contribute to collections of yeast synthetic biology parts available to the scientific community. This research will also develop methods for high-throughput strain engineering in this understudied yet important class of organisms.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.

已经发现不同类型的微生物能够产生以前从未见过的化学物质和功能，以便充分利用它们的能力。该研究项目的重点是为特定类型的微生物开发此类工具。一种名为 Xanthophyllomyces dendrorhous 的酵母，通常被称为红酵母，因其能够产生虾青素而被选中进行研究，虾青素是一种与 β-胡萝卜素相关的抗氧化剂，在治疗许多疾病方面取得了一些成功。利用红酵母制造这种分子的能力，将能够生产大量具有广泛用途的相关化合物。参与该项目的研究生将接受培训。通过课程开发、实验室研究和继续教育项目，随着合成生物学创新的快速发展继续改变生物制造，这些努力将为下一代工程师做好准备。该研究项目涉及使用基因组学方法来理解和设计担子菌酵母，树状叶黄酵母（Xanthophyllomyces dendrorhous），通常被称为红酵母，红酵母具有遗传易驯化性，通常被认为是安全的，并且用于生产萜类虾青素，因为它可以产生几乎所有萜类化合物的前体库。这项研究的目的是使用红酵母作为宿主，为几种不同的有价值的化合物创建一个萜类细胞工厂，用于研究遗传基础。独特的基因调控和光生物学的目标是利用高通量组合菌株工程方法来同时修改宿主和异源途径，以提高萜类化合物的效价和生产力。这项研究还将开发用于这一尚未充分研究但重要的生物体类别的高通量菌株工程方法。该奖项反映了 NSF 的贡献。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。