Complete biosynthesis of QS-21 in engineered yeast

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…

• UD
  U.S. Department of Energy

  Awards: -AC02-05CH11231, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
• UD
  U.S. Department of Commerce

  Award: 70NANB22H017
• JI
  John Innes Foundation
• NI
  National Institutes of Health

  Awards: 1S10OD020062-01, 1S10OD020062, DE-AC02-05CH11231
• DF
  Directorate for Biological Sciences
• NI
  National Institute of Standards and Technology

  Awards: DE-AC02-05CH11231, 70NANB22H017
• OO
  Office of Science

  Awards: AC02-05CH11231, -AC02-05CH11231, DE-AC02
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/R005508/1, BBS/E/JI/230004B
• LB
  Lawrence Berkeley National Laboratory

  Awards: DE-AC02-05CH11231, 05CH11231, AC02-05CH11231