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Related Experiment Video

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Identification of Functional Protein Regions Through Chimeric Protein Construction
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Constructing Yeast Chimeric Pathways To Boost Lipophilic Terpene Synthesis.

Duo Liu1,2, Hong Liu1,2, Hao Qi1,2

  • 1Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology , Tianjin University , Tianjin 300350 , P. R. China.

ACS Synthetic Biology
|February 20, 2019
PubMed
Summary

Synthetic biology enables pathway construction for enhanced production. Yeast chimeric pathways, particularly the mevalonic acid (MVA) pathway, significantly boosted lycopene synthesis by 150-fold.

Keywords:
DNA assemblySaccharomyces cerevisiaeYarrowia lipolyticasynthetic biologyterpenetranscriptional unit

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Area of Science:

  • Synthetic biology
  • Metabolic engineering
  • Yeast biotechnology

Background:

  • Synthetic chimeric biological systems offer insights into designing life.
  • Constructing synthetic chimeric pathways is a crucial first step.
  • Transferring genes between yeast species facilitates in vivo assembly.

Purpose of the Study:

  • To construct yeast chimeric pathways by transferring genes from Saccharomyces cerevisiae to Yarrowia lipolytica.
  • To investigate the impact of gene combination, localization, and copy number on synthetic pathway performance.
  • To enhance the production of lipophilic compounds, specifically lycopene.

Main Methods:

  • Gene transfer and in vivo assembly of Saccharomyces cerevisiae pathways into Yarrowia lipolytica.
  • Diversification of gene options, combinations, localization order, and copy numbers.
  • Metabolic engineering and optimization of the mevalonic acid (MVA) pathway for enhanced lycopene production.

Main Results:

  • Chimeric mevalonic acid (MVA) pathways significantly enhanced lycopene synthesis.
  • A champion strain with a chimeric MVA pathway achieved a 50-fold increase in lycopene production.
  • Further modulation of related pathways led to a 150-fold increase, reaching 259 mg/L lycopene.
  • Distinct transcriptional up-regulation of acetyl-CoA supply and lipid metabolism pathways was observed.

Conclusions:

  • Yeast chimeric pathways are effective for boosting the synthesis of lipophilic products.
  • Optimization of synthetic pathways, including gene context and cellular metabolism, is key to high-yield production.
  • This study demonstrates a powerful strategy for engineering microbial cell factories for valuable compound synthesis.