QS-21 is a complex plant natural product that enhances the ability of the immune system to respond to vaccine antigens. As such, it is an active component of the FDA-approved Shingrix shingles vaccine and currently under clinical evaluation as an additive for various trial vaccines, including those for HIV, malaria, and SARS-CoV-2. However, the isolation of QS-21 destroys the soap bark trees and therefore, has resulted in regulation by the local government. In order to make QS-21 in yeast, we first investigated the biosynthesis of the QS-21 triterpene core, quillaic acid using a combinatorial strategy of co-expressing heterologous cyclases, and P450s in the strain that has an upregulated mevalonate pathway. Seven sequential glycosylation steps were achieved via the expression of nucleotide sugar synthases and corresponding transferases of plant origins. A total of 36 heterologous pathway proteins were expressed spanning across P450s, polyketide synthases, and glycosyltransferases. Because of enzymes’ high specificity, functional groups as well as saccharides can be selectively added to carbon positions of choice, forgoing the need to detour synthetic steps to ensure stereo- and chemoselectivity. Our strategy provides a simple yet versatile platform to provide a renewable and consistent production of bioactive saponins, which constitute a large and structurally diverse class of natural products towards various industrial and pharmaceutical applications.

The complete biosynthesis of Qs-21, a potent vaccine adjuvant in engineered yeast

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.