Production of lovastatin and itaconic acid by Aspergillus terreus: a comparative perspective

Abstract

Aspergillus terreus is a textbook example of an industrially relevant filamentous fungus. It is used for the biotechnological production of two valuable metabolites, namely itaconic acid and lovastatin. Itaconic acid serves as a precursor in polymer industry, whereas lovastatin found its place in the pharmaceutical market as a cholesterol-lowering statin drug and a precursor for semisynthetic statins. Interestingly, their biosynthetic gene clusters were shown to reside in the common genetic neighborhood. Despite the genomic proximity of the underlying biosynthetic genes, the production of lovastatin and itaconic acid was shown to be favored by different factors, especially with respect to pH values of the broth. While there are several reviews on various aspects of lovastatin and itaconic acid production, the survey on growth conditions, biochemistry and morphology related to the formation of these two metabolites has never been presented in the comparative manner. The aim of the current review is to outline the correlations and contrasts with respect to process-related and biochemical discoveries regarding itaconic acid and lovastatin production by A. terreus.

Keywords: Aspergillus terreus; Itaconic acid; Lovastatin; Metabolites.

Fig. 1

Pathways of itaconic acid (a) and lovastatin (b) biosynthesis in Aspergillus terreus (Ames et al. ; Bentley and Thiessen ; Kennedy et al. ; Steiger et al. 2013). The enzymes participating in the respective steps are indicated. The catalytic domains of lovastatin nonaketide synthase LovB are shown in brackets. ACP acyl carrier protein; AT acyltransferase; CadA cis-aconitic acid decarboxylase; DH dehydratase; KS β-ketoacyl synthase; KR ketoreductase; LovA cytochrome P450 monooxygenase; LovB lovastatin nonaketide synthase; LovC enoyl reductase; LovD acyl transferase; LovF lovastatin diketide synthase; mal-CoA malonyl-CoA; MT methyltransferase