Genome editing approaches: manipulating of lovastatin and taxol synthesis of filamentous fungi by CRISPR/Cas9 system.

ABSTRACT

Filamentous fungi are prolific repertoire of structurally diverse secondary metabolites of remarkable biological activities such as lovastatin and paclitaxel that have been approved by FDA as drugs for hypercholesterolemia and cancer treatment. The clusters of genes encoding lovastatin and paclitaxel are cryptic at standard laboratory cultural conditions (Kennedy et al. Science 2841368-1372, 1999; Bergmann et al. Nature Chem Biol 3213-217, 2007). The expression of these genes might be triggered in response to nutritional and physical conditions; nevertheless, the overall yield of these metabolites does not match the global need. Consequently, overexpression of the downstream limiting enzymes and/or blocking the competing metabolic pathways of these metabolites could be the most successful technologies to enhance their yield. This is the first review summarizing the different strategies implemented for fungal genome editing, molecular regulatory mechanisms, and prospective of clustered regulatory interspaced short palindromic repeat/Cas9 system in metabolic engineering of fungi to improve their yield of lovastatin and taxol to industrial scale. Thus, elucidating the putative metabolic pathways in fungi for overproduction of lovastatin and taxol was the ultimate objective of this review.