Role of acetyl-CoA Synthetase and LovE Regulator Protein of Polyketide Biosynthesis in Lovastatin Production by Wild-Type and Overproducing Aspergillus terreus Strains

Abstract

The expression of two key genes of lovastatin (LOV) biosynthesis has been studied in two Aspergillus terreus strains characterized by a more than hundredfold difference in the LOV yield. As compared to the wild-type strain ATCC 20542, in the overproducing strain 43-16 significantly enhanced expression level of LOV biosynthetic genes (by 5–50 times), transcription factor lovE (by 3–20 times), and the acs gene, which encodes acetyl-CoA synthetase (by two times), was detected. To improve the efficiency of LOV biosynthesis, recombinant A. terreus strains constitutively expressing the ACS1 gene from Saccharomyce scerevisiae or the lovE gene from A. terreus have been designed by metabolic engineering methods. According to the obtained results, the expression of ACS1 in strain 43-16 results in the suppression of lovC and lovD production and a more than 25% reduction of LOV production. In the case of low-active ATCC 20542/ACS1 recombinants, the expression level of lov genes remains almost unchanged, while the expression of the endogenous asc1 gene is enhanced and the LOV yield increases by 117%. Constitutive overexpression of the lovE gene in the ATCC 20452 strain results in the increase of mRNA levels of biosynthetic lov-genes and is accompanied by a significant (6–10 times) increase in the LOV yield.