UPM Institutional Repository

Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus


Hasan, Hanan and Abd Rahim, Muhamad Hafiz and Campbell, Leona and Carter, Dee and Montoya, Alejandro and Abbas, Ali (2019) Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus. New Biotechnology, 52. pp. 19-24. ISSN 1871-6784; ESSN: 1876-4347


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.

Download File

[img] Text (Abstract)
Improved lovastatin production by inhibiting (+)-geodin biosynthesis in aspergillus terreus.pdf

Download (105kB)
Official URL or Download Paper: https://pubmed.ncbi.nlm.nih.gov/30995533/

Additional Metadata

Item Type: Article
Divisions: Faculty of Food Science and Technology
DOI Number: https://doi.org/10.1016/j.nbt.2019.04.003
Publisher: Elsevier BV
Keywords: (+)-Geodin; Aspergillus terreus; Emodin anthrone polyketide synthase; Gene knockout; Lovastatin
Depositing User: Azhar Abdul Rahman
Date Deposited: 01 Oct 2020 07:29
Last Modified: 01 Oct 2020 07:29
Altmetrics: http://altmetrics.com-details.php?domain=psair.upm.edu.my&doi= 10.1016/j.nbt.2019.04.003
URI: http://psasir.upm.edu.my/id/eprint/80185
Statistic Details: View Download Statistic

Actions (login required)

View Item View Item