Cloning and Characterization of Monacolin K Biosynthetic Gene Cluster from Monascus pilosus

Abstract

Monacolin K is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus, and it has the same structure as lovastatin, which is mainly produced by Aspergillus terreus. In the present study, a bacterial artificial chromosome (BAC) clone, mps01, was screened from the BAC library constructed from Monascus pilosus BCRC38072 genomic DNA. The putative monacolin K biosynthetic gene cluster was found within a 42 kb region in the mps01 clone. The deduced amino acid sequences encoded by the nine genes designated as mokA- mokI, which share over 54% similarity with the lovastatin biosynthetic gene cluster in A. terreus, were assumed to be involved in monacolin K biosynthesis. A gene disruption construct designed to replace the central part of mokA, a polyketide synthase gene, in wild-type M. pilosus BCRC38072 with a hygromycin B resistance gene through homologous recombination, resulted in a mokA-disrupted strain. The disruptant did not produce monacolin K, indicating that mokA encoded the PKS responsible for monacolin K biosynthesis in M. pilosus BCRC38072.

Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis

“…1A; tetra-, penta-, and heptaketides). Similar trans-acting ERs have also been reported in other fungi such as MokE in Monascus pilosus (8), MlcG in Penicillium citrinum (9), ApdC in Aspergilus nidulans (10-12), cytochalasans (12,13), and tenellin_ORF3 in Beauveria bassiana (14). These trans-acting ERs are highly homologous (38-80% sequence identity; Fig.…”

Microbiota associated with the starter cultures and brewing process of traditional Hong Qu glutinous rice wine

“…It was reported that citrinin could cause cell death to human embryonic kidney cells in a range of 1.8-4.7 mg/mL (94). According to animal tests, it was proposed that less than 2 ppm citrinin in Monascusfermented products might be a safe concentration (95,96). However, Hong Qu rice wine has been used as traditional rice wine without a reported or known case of undesirable effects because of the low concentrations in the rice wine products.…”

Lovastatin, Compactin, and Related Anticholesterolemic Agents

“…Concurrent programs focused on isolating the gene clusters responsible for the biosynthesis of compactin in P. citrinum [ 54 ] and also for lovastatin from an alternate lovastatin producing species, Monascus pilosus [ 55 ]. Not surprisingly, the overall architecture of these two gene clusters ( mlc and mok respectively) has high homology to the lov system.…”