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Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum.

Nadja A Henke1, Julian Wichmann2, Thomas Baier3

  • 1Genetics of Prokaryotes, Faculty of Biology & CeBiTec, Bielefeld University, D-33615 Bielefeld, Germany. n.henke@uni-bielefeld.de.

Genes
|April 21, 2018
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Summary

This study engineered *Corynebacterium glutamicum* to produce patchoulol, a valuable perfume ingredient. The engineered strain achieved record-high patchoulol titers using advanced metabolic engineering and fermentation techniques.

Keywords:
Corynebacterium glutamicumEscherichia colialgaemetabolic engineeringpatchoulolsesquiterpene

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Area of Science:

  • Microbial biotechnology
  • Metabolic engineering
  • Synthetic biology

Background:

  • Patchoulol is a key sesquiterpene alcohol for the perfume industry.
  • *Corynebacterium glutamicum* is a robust industrial host for fermentative production, previously engineered for carotenoids and other terpenes.
  • Developing microbial production of patchoulol offers a sustainable alternative to plant extraction.

Purpose of the Study:

  • To engineer a *Corynebacterium glutamicum* strain for efficient patchoulol production.
  • To optimize precursor supply and heterologous gene expression for sesquiterpene synthesis.
  • To demonstrate high-titer patchoulol production using a novel fermentation system.

Main Methods:

  • Systematic metabolic engineering of *C. glutamicum* including genomic deletions and heterologous gene expression.
  • Optimization of the 2-c-methyl-d-erythritol 4-phosphate (MEP) pathway and farnesyl pyrophosphate (FPP) precursor supply.
  • Heterologous expression of the patchoulol synthase gene (*Pc*PS) from *Pogostemon cablin*.
  • Fermentation using a two-phase organic overlay culture system for product capture.

Main Results:

  • A *C. glutamicum* strain capable of producing patchoulol was successfully constructed.
  • Achieved patchoulol titers up to 60 mg/L and volumetric productivities up to 18 mg/L/day.
  • Demonstrated prevention of carotenoid byproduct formation and enhanced precursor availability.
  • Successful proof-of-principle fermentation showcasing the effectiveness of the two-phase culture system.

Conclusions:

  • Metabolic engineering of *C. glutamicum* is a viable strategy for producing the high-value fragrance compound patchoulol.
  • The developed strain and fermentation process represent a significant advancement in microbial terpene production.
  • This work paves the way for sustainable and scalable biotechnological production of patchoulol.