酵母で作られたアジュバントはワクチンコストを下げ、入手可能性を高める可能性がある(An adjuvant made in yeast could lower vaccine cost and boost availability)

2024-05-08 カリフォルニア大学バークレー校(UCB)

<関連情報>

• https://news.berkeley.edu/2024/05/08/an-adjuvant-made-in-yeast-could-lower-vaccine-cost-and-boost-availability
• https://www.nature.com/articles/s41586-024-07345-9

人工酵母によるQS-21の完全生合成 Complete biosynthesis of QS-21 in engineered yeast

Yuzhong Liu,Xixi Zhao,Fei Gan,Xiaoyue Chen,Kai Deng,Samantha A. Crowe,Graham A. Hudson,Michael S. Belcher,Matthias Schmidt,Maria C. T. Astolfi,Suzanne M. Kosina,Bo Pang,Minglong Shao,Jing Yin,Sasilada Sirirungruang,Anthony T. Iavarone,James Reed,Laetitia B. B. Martin,Amr El-Demerdash,Shingo Kikuchi,Rajesh Chandra Misra,Xiaomeng Liang,Michael J. Cronce,Xiulai Chen,… Jay D. Keasling
Nature  Published:08 May 2024
DOI:https://doi.org/10.1038/s41586-024-07345-9

Abstract

QS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans^1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis^3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host’s native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families—a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases—from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure–activity relationship, and will thus enable the rational design of potent vaccine adjuvants.