초록
<P><B>Abstract</B></P> <P>The present work describes the application of homologous recombination techniques in a wild-type <I>Aspergillus terreus</I> (<B>ATCC 20542</B>) 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 P<I>adhA</I> promoter from <I>Aspergillus nidulans</I>. Glycerol and a mixture of lactose and glycerol were used independently as the carbon feedstock to determine the degree of response by the <I>A. terreus</I> 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 <I>Aspergillus terreus</I> can be manipulated to attain higher levels of precursors and valuable secondary metabolites.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The overexpression of acetyl-CoA carboxylase (ACCase) in <I>Aspergillus terreus</I>. </LI> <LI> Increasing level of malonyl-CoA and acetyl-CoA due to the overexpression of ACCase. </LI> <LI> Change in precursors level affects lovastatin and (+)-geodin production. </LI> <LI> Varying substrates on mutant strain can promote lovastatin and suppress (+)-geodin. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P> <I>Aspergillus terreus</I> has the ability to produce cholesterol-lowering drug, lovastatin but the yield is not fully maximize. A new engineered <I>A. terreus</I> strain was developed to overexpress acetyl-CoA carboxylase by inserting strong promoter P<I>adhA</I> (isolated from <I>Aspergillus nidulans</I>). 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.</P> <P>[DISPLAY OMISSION]</P>