Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production

The present work describes the application of homologous recombination techniques in a wild-type Aspergillus terreus (ATCC 20542) strain to increase the flow of precursors towards the lovastatin biosynthesis pathway. A new strain was generated to overexpress acetyl-CoA carboxylase (ACCase) by replac...

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Main Authors: Hasan, Hanan, Abd Rahim, Muhammad Hafiz, Campbell, Leona, Carter, Dee, Abbas, Ali, Montoya, Alejandro
Format: Article
Language:English
Published: Elsevier 2018
Online Access:http://psasir.upm.edu.my/id/eprint/75182/
http://psasir.upm.edu.my/id/eprint/75182/1/Overexpression.pdf
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author Hasan, Hanan
Abd Rahim, Muhammad Hafiz
Campbell, Leona
Carter, Dee
Abbas, Ali
Montoya, Alejandro
author_facet Hasan, Hanan
Abd Rahim, Muhammad Hafiz
Campbell, Leona
Carter, Dee
Abbas, Ali
Montoya, Alejandro
author_sort Hasan, Hanan
building UPM Institutional Repository
collection Online Access
description The present work describes the application of homologous recombination techniques in a wild-type Aspergillus terreus (ATCC 20542) strain to increase the flow of precursors towards the lovastatin biosynthesis pathway. A new strain was generated to overexpress acetyl-CoA carboxylase (ACCase) by replacing the native ACCase promoter with a strong constitutive PadhA promoter from Aspergillus nidulans. Glycerol and a mixture of lactose and glycerol were used independently as the carbon feedstock to determine the degree of response by the A. terreus strains towards the production of acetyl-CoA, and malonyl-CoA. The new strain increased the levels of malonyl-CoA and acetyl-CoA by 240% and 14%, respectively, compared to the wild-type strain. As a result, lovastatin production was increased by 40% and (+)-geodin was decreased by 31% using the new strain. This study shows for the first time that the metabolism of Aspergillus terreus can be manipulated to attain higher levels of precursors and valuable secondary metabolites.
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spelling upm-751822021-09-08T09:22:46Z http://psasir.upm.edu.my/id/eprint/75182/ Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production Hasan, Hanan Abd Rahim, Muhammad Hafiz Campbell, Leona Carter, Dee Abbas, Ali Montoya, Alejandro The present work describes the application of homologous recombination techniques in a wild-type Aspergillus terreus (ATCC 20542) strain to increase the flow of precursors towards the lovastatin biosynthesis pathway. A new strain was generated to overexpress acetyl-CoA carboxylase (ACCase) by replacing the native ACCase promoter with a strong constitutive PadhA promoter from Aspergillus nidulans. Glycerol and a mixture of lactose and glycerol were used independently as the carbon feedstock to determine the degree of response by the A. terreus strains towards the production of acetyl-CoA, and malonyl-CoA. The new strain increased the levels of malonyl-CoA and acetyl-CoA by 240% and 14%, respectively, compared to the wild-type strain. As a result, lovastatin production was increased by 40% and (+)-geodin was decreased by 31% using the new strain. This study shows for the first time that the metabolism of Aspergillus terreus can be manipulated to attain higher levels of precursors and valuable secondary metabolites. Elsevier 2018 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/75182/1/Overexpression.pdf Hasan, Hanan and Abd Rahim, Muhammad Hafiz and Campbell, Leona and Carter, Dee and Abbas, Ali and Montoya, Alejandro (2018) Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production. New Biotechnology, 44. 64 - 71. ISSN 1871-6784; ESSN: 1876-4347 https://www.sciencedirect.com/science/article/abs/pii/S1871678417306763?via%3Dihub 10.1016/j.nbt.2018.04.008
spellingShingle Hasan, Hanan
Abd Rahim, Muhammad Hafiz
Campbell, Leona
Carter, Dee
Abbas, Ali
Montoya, Alejandro
Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title_full Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title_fullStr Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title_full_unstemmed Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title_short Overexpression of acetyl-CoA carboxylase in Aspergillus terreus to increase lovastatin production
title_sort overexpression of acetyl-coa carboxylase in aspergillus terreus to increase lovastatin production
url http://psasir.upm.edu.my/id/eprint/75182/
http://psasir.upm.edu.my/id/eprint/75182/
http://psasir.upm.edu.my/id/eprint/75182/
http://psasir.upm.edu.my/id/eprint/75182/1/Overexpression.pdf