CAREER: A Red Yeast Cell Factory

已经发现不同类型的微生物产生化合物，并以以前从未见过的活性水平发挥作用。 必须开发新的遗传工具，以便充分利用它们的能力。 该研究项目的重点是为一种名为Xanthophyllomyces dendrorhous的特定类型的酵母（通常称为红酵母）开发此类工具。选择这种生物进行研究是因为它能够产生虾青素，一种与β-胡萝卜素相关的抗氧化剂。虾青素在治疗许多疾病方面取得了一些成功，包括阿尔茨海默氏症、帕金森氏症、高胆固醇和糖尿病。利用红酵母制造这种分子的能力将能够生产大量相关化合物，这些化合物可能具有广泛的用途。 参与该项目的研究生将通过课程开发，实验室研究和继续教育计划进行培训。这些努力将为下一代工程师做好准备，因为合成生物学创新的快速步伐将继续改变生物制造业。该研究项目涉及使用基因组学方法来理解和设计一种担子菌酵母，Xanthophyllomyces dendrorhous，通常被称为红酵母。红酵母在遗传上是易处理的，通常被认为是安全的，并用于制造萜类虾青素。 这种生物体有希望作为萜类化合物生产平台，因为它产生几乎所有萜类化合物的前体库。本研究的一个主要目的是利用红酵母作为宿主，建立一个萜类化合物的细胞工厂。转录组学将用于研究独特的基因调控和光生物学的遗传基础。我们的目标是利用高通量组合菌株工程方法来利用这些独特的性状。该过程将同时修饰宿主和异源途径以提高萜类化合物滴度和生产率。沿着的方式，该项目将推进担子菌工程策略，并有助于收集酵母合成生物学部分提供给科学界。这项研究还将开发高通量菌株工程的方法，在这一研究不足，但重要的一类organism.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.