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

Aspergillus terreus has the ability to produce cholesterol-lowering drug, lovastatin but the yield is not fully maximize. A new engineered A. terreus strain was developed to overexpress acetyl-CoA carboxylase by inserting strong promoter PadhA (isolated from Aspergillus nidulans). When the engineere...

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Bibliographic Details
Published in:	New biotechnology 2018-09, Vol.44, p.64-71
Main Authors:	Hasan, Hanan, Abd Rahim, Muhammad Hafiz, Campbell, Leona, Carter, Dee, Abbas, Ali, Montoya, Alejandro
Format:	Article
Language:	eng
Subjects:	Acetyl-CoA carboxylase Aspergillus terreus Biosynthesis Chemical compounds Fungi Geodin Glycerol Glycerols Homologous recombination Homology Lactose Lovastatin Metabolism Metabolites Overexpression Precursors Secondary metabolites
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Summary:	Aspergillus terreus has the ability to produce cholesterol-lowering drug, lovastatin but the yield is not fully maximize. A new engineered A. terreus strain was developed to overexpress acetyl-CoA carboxylase by inserting strong promoter PadhA (isolated from Aspergillus nidulans). When the engineered strain grew in a mixture of glycerol (low value feedstock) and lactose, the malonyl-CoA and acetyl-CoA (lovastatin precursors) levels were amplified and positively affect lovastatin production while suppressing unwanted lovastatin co-product, (+)-geodin. [Display omitted] •The overexpression of acetyl-CoA carboxylase (ACCase) in Aspergillus terreus.•Increasing level of malonyl-CoA and acetyl-CoA due to the overexpression of ACCase.•Change in precursors level affects lovastatin and (+)-geodin production.•Varying substrates on mutant strain can promote lovastatin and suppress (+)-geodin. 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.
ISSN:	1871-6784 1876-4347