Increasing Lovastatin Production by Re-routing the Precursors Flow of Aspergillus terreus via Metabolic Engineering

Hasan H 1 , Abd Rahim MH 2 , Campbell L 3 , Carter D 3 , Abbas A 2 , Montoya A 2

Affiliations 

  • 1 School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, Australia. mhanan@upm.edu.my
  • 2 School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, Australia
  • 3 School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia
Mol Biotechnol, 2022 Jan;64(1):90-99.
PMID: 34546548 DOI: 10.1007/s12033-021-00393-w

Abstract

Lovastatin is an anti-cholesterol medicine that is commonly prescribed to manage cholesterol levels, and minimise the risk of suffering from heart-related diseases. Aspergillus terreus (ATCC 20542) supplied with carbohydrates or sugar alcohols can produce lovastatin. The present work explored the application of metabolic engineering in A. 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 flux, and eliminate ( +)-geodin biosynthesis (a competing secondary metabolite) by removing the gene for 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. The gedCΔ*accox strain, when cultivated with a mixture of glycerol and lactose, significantly (p 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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