CAREER: A Red Yeast Cell Factory

Worcester Polytechnic Institute, Worcester MA

Investigators

Abstract

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.