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

• 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/75182/1/Overexpression.pdf; http://psasir.upm.edu.my/id/eprint/75182/; https://www.sciencedirect.com/science/article/abs/pii/S1871678417306763?via%3Dihub

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.