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Engineering Aspergillus terreus Metabolic Pathways to Increase Lovastatin Production via Metabolic Engineering and Fermentation Approaches
  • +3
  • Hanan Hasan,
  • Muhammad Hafiz Abd Rahim,
  • Leona CampbellOrcid,
  • Dee Carter,
  • Ali Abbas,
  • Alejandro Montoya
Hanan Hasan
University Putra Malaysia
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Muhammad Hafiz Abd Rahim
University Putra Malaysia
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Leona Campbell
Orcid
University of Sydney
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Dee Carter
University of Sydney
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Ali Abbas
The University of Sydney, University of Sydney
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Alejandro Montoya
The University of Sydney
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Peer review status:UNDER REVIEW

23 Jun 2020Submitted to Biotechnology and Bioengineering
23 Jun 2020Assigned to Editor
23 Jun 2020Submission Checks Completed
08 Jul 2020Review(s) Completed, Editorial Evaluation Pending

Abstract

This study explores the application of metabolic engineering in Aspergillus terreus to re-route the precursor flow towards the lovastatin biosynthetic pathway by simultaneously overexpressing the gene for acetyl-CoA carboxylase (acc) to increase the precursor and eliminating (+)-geodin biosynthesis (competing metabolite), by knocking out emodin anthrone polyketide synthase (gedC). Alterations to metabolic flux in the double mutant (gedCΔ*accox) strain and the effects of using two different substrate formulations were examined. Cultivation of gedCΔ*accox strain with a mixture of glycerol and lactose, had greatly increased levels of precursors malonyl-CoA (48%) and acetyl-CoA (420%), complete inhibition of (+)-geodin biosynthesis and a maximum production of lovastatin (152 mg/L), 143% more than the wild-type (WT) strain. This study demonstrates the manipulation of A. terreus metabolic pathways to increase the efficiency of carbon flux towards lovastatin, elevating its production. It provides a framework for new opportunities to synthesize valuable compounds using cheap and renewable carbon sources.