Production of the antidepressant orcinol glucoside in Yarrowia lipolytica with yields over 6,400-fold higher than plant extraction

PLoS Biol. 2023 Jun 6;21(6):e3002131. doi: 10.1371/journal.pbio.3002131. eCollection 2023 Jun.

Abstract

Orcinol glucoside (OG), mainly found in the rhizome of the traditional Chinese herb Curculigo orchioides Gaertn, is noted for its antidepressant effects. In this study, an efficient screening pipeline was established for identifying the highly active orcinol synthase (ORS) and UDP-dependent glycosyltransferase (UGT) involved in the biosynthesis of OG by combining transcriptome analysis, structure-based virtual screening, and in vitro enzyme activity assays. By enhancing the downstream pathway, metabolic engineering and fermentation optimization, the OG production in Yarrowia lipolytica was improved 100-fold, resulting in a final yield of 43.46 g/L (0.84 g/g DCW), which is almost 6,400-fold higher than the extraction yield from C. orchioides roots. This study provides a reference for rapid identification of functional genes and high-yield production of natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fermentation
  • Glucosides* / metabolism
  • Metabolic Engineering / methods
  • Yarrowia* / genetics

Substances

  • Glucosides
  • orcinol

Grants and funding

This work was supported by the Major Science and Technology Projects of Yunnan Province (202102AA310048-1 to SY), the Science and Technology Innovation Team of Yunnan (202105AE160011 to SY), the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory (2022YKZY001 to SY), the Major Science and Technology Programs in Yunnan Province (2018ZF011 and 202102AA310045 to SZ), the Tianjin Science Fund for Distinguished Young Scholars (18JCJQJC48300 to HJ), Science and Technology Partnership Program, Ministry of Science and Technology of China (KY202001017 to HJ), COMSATS Joint Center for Industrial Biotechnology (TSBICIP-IJCP-001-01 to HJ) and National Key R&D Program of China (Grant No. 2021YFC2103500 to HJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.