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Complete biosynthesis of QS-21 in engineered yeast
Yuzhong Liu1,2, Xixi Zhao1,2, Fei Gan1,2
1California Institute of Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.
Nature
|May 8, 2024
Summary
Scientists engineered yeast to produce QS-21, a crucial vaccine adjuvant, through complete biosynthesis. This microbial production overcomes supply limitations of the complex saponin, enabling future adjuvant design.
Area of Science:
- Biotechnology
- Chemical Biology
- Vaccinology
Background:
- QS-21 is a clinically approved saponin-based vaccine adjuvant with limited availability due to complex extraction and synthesis.
- Current supply relies on laborious tree extraction or low-yield chemical synthesis, hindering widespread use.
Purpose of the Study:
- To establish a complete biosynthetic pathway for QS-21 and its precursors in engineered yeast.
- To develop a sustainable microbial production platform for QS-21 and its derivatives.
- To enable the rational design of novel, potent vaccine adjuvants.
Main Methods:
- Engineered yeast strains were developed to express 38 heterologous enzymes from six different organisms.
- The biosynthetic pathway mimicked plant subcellular compartmentalization, involving enzymes from terpene synthases to polyketide synthases.
- Enzyme promiscuity was utilized to produce structural analogues of QS-21.
Main Results:
- Complete biosynthesis of QS-21 and its precursors was achieved in engineered yeast.
- The engineered yeast successfully produced structural analogues of QS-21.
- This microbial platform demonstrates a viable alternative to traditional QS-21 production methods.
Conclusions:
- Microbial biosynthesis provides a scalable and sustainable method for producing QS-21 and related compounds.
- This platform facilitates structure-activity relationship studies for the rational design of improved vaccine adjuvants.
- The engineered yeast represents a significant advancement in adjuvant production and vaccine development.
