Production of abscisic acid in the oleaginous yeast Yarrowia lipolytica

Jonathan Asmund Arnesen, Irene Hjorth Jacobsen, Jane Dannow Dyekjær, Daniela Rago, Mette Kristensen, Andreas Koedfoed Klitgaard, Milica Randelovic, José Luis Martinez, Irina Borodina*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Abscisic acid (ABA) is a phytohormone with applications in agriculture and human health. ABA can be produced by Botrytis cinerea, a plant pathogenic filamentous fungus. However, the cultivation process is lengthy and strain improvement by genetic engineering is difficult. Therefore, we engineered the oleaginous yeast Yarrowia lipolytica as an alternative host for ABA production. First, we expressed five B. cinerea genes involved in ABA biosynthesis (BcABA1, BcABA2, BcABA3, BcABA4, and BcCPR1) in a Y. lipolytica chassis with optimized mevalonate flux. The strain produced 59.2 mg/L of ABA in small-scale cultivation. Next, we expressed an additional copy of each gene in the strain, but only expression of additional copy of BcABA1 gene increased the ABA titer to 168.5 mg/L. We then integrated additional copies of mevalonate pathway and ABA-biosynthesis encoding genes, and we expressed plant ABA-transporters resulting in an improved strain producing 263.5 mg/L and 9.1 mg/g DCW ABA. Bioreactor cultivation resulted in a specific yield of 12.8 mg/g DCW ABA, however, surprisingly, the biomass level obtained in bioreactors was only 10.5 g DCW/L, with a lower ABA titer of 133.6 mg/L. While further optimization is needed, this study confirms that Y. lipolytica as a potential alternative host for the abscisic acid production.
Original languageEnglish
Article numberfoac015
JournalFEMS Yeast Research
ISSN1567-1356
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • Abscisic acid
  • Yarrowia lipolytica
  • Terpenoids
  • Yeast
  • Isoprenoids

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