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Engineering Aspergillus terreus Metabolic Pathways to Increase Lovastatin Production via Metabolic Engineering and Fermentation Approaches

      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.

      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