Affiliations 

  • 1 The University of Sydney, School of Chemical and Biomolecular Engineering, Australia; Universiti Putra Malaysia, Faculty of Food Science and Technology, Malaysia. Electronic address: mhanan@upm.edu.my
  • 2 The University of Sydney, School of Chemical and Biomolecular Engineering, Australia; Universiti Putra Malaysia, Faculty of Food Science and Technology, Malaysia
  • 3 The University of Sydney, School of Life and Environmental Sciences, Australia
  • 4 The University of Sydney, School of Chemical and Biomolecular Engineering, Australia
N Biotechnol, 2019 Sep 25;52:19-24.
PMID: 30995533 DOI: 10.1016/j.nbt.2019.04.003

Abstract

Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity.

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