Metabolite trafficking enables membrane-impermeable-terpene secretion by yeast

So-Hee Son, Jae-Eung Kim, Gyuri Park, Young-Joon Ko, Bong Hyun Sung, Jongcheol Seo, Seung Soo Oh () and Ju Young Lee ()
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So-Hee Son: Korea Research Institute of Chemical Technology (KRICT)
Jae-Eung Kim: Korea Research Institute of Chemical Technology (KRICT)
Gyuri Park: Pohang University of Science and Technology (POSTECH)
Young-Joon Ko: Korea Research Institute of Chemical Technology (KRICT)
Bong Hyun Sung: Korea Research Institute of Bioscience and Biotechnology (KRIBB)
Jongcheol Seo: Pohang University of Science and Technology (POSTECH)
Seung Soo Oh: Pohang University of Science and Technology (POSTECH)
Ju Young Lee: Korea Research Institute of Chemical Technology (KRICT)

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Metabolites are often unable to permeate cell membranes and are thus accumulated inside cells. We investigate whether engineered microbes can exclusively secrete intracellular metabolites because sustainable metabolite secretion holds a great potential for mass-production of high-value chemicals in an efficient and continuous manner. In this study, we demonstrate a synthetic pathway for a metabolite trafficking system that enables lipophilic terpene secretion by yeast cells. When metabolite-binding proteins are tagged with signal peptides, metabolite trafficking is highly achievable; loaded metabolites can be precisely delivered to a desired location within or outside the cell. As a proof of concept, we systematically couple a terpene-binding protein with an export signal peptide and subsequently demonstrate efficient, yet selective terpene secretion by yeast (~225 mg/L for squalene and ~1.6 mg/L for β-carotene). Other carrier proteins can also be readily fused with desired signal peptides, thereby tailoring different metabolite trafficking pathways in different microbes. To the best of our knowledge, this is the most efficient cognate pathway for metabolite secretion by microorganisms.

Date: 2022
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DOI: 10.1038/s41467-022-30312-9

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