Production of Monacolin K in Monascus pilosus: Comparison between Industrial Strains and Analysis of Its Gene Clusters

Monascus pilosus strains are widely applied to yield a cholesterol synthesis inhibitor monacolin K (MK), also called lovastatin (LOV). However, the mechanism of MK production by M. pilosus strains is still unclear. In this study, we firstly confirmed four Monascus strains, MS-1, YDJ-1, YDJ-2, and K104061, isolated from commercial MK products as M. pilosus and compared their abilities to produce MK in solid-state and liquid-state cultures. Then, we sequenced and analyzed their genomes and MK biosynthetic gene clusters (BGCs). The results revealed that the MK yields of MS-1, YDJ-1, YDJ-2, and K104061 in solid-state cultures at 14 days were 6.13, 2.03, 1.72, and 0.76 mg/g, respectively; the intracellular and extracellular MK contents of MS-1, YDJ-1, YDJ-2, and K104061 in liquid-state cultures at 14 days reached 0.9 and 1.8 mg/g, 0.38 and 0.43 mg/g, 0.30 and 0.42 mg/g, and 0.31 and 0.76 mg/g, respectively. The genome sizes of the four M. pilosus strains were about 26 Mb, containing about 7000-8000 coding genes and one MK gene cluster. The MK BGCs of MS-1, YDJ-2, and K104061 contained 11 genes, and the MK BGC of YDJ-1 contained 9 genes. According to the literature search, there are few comparisons of gene clusters and related genes responsible for the synthesis of LOV and MK. We also compared the LOV BGC in A. terreus with the MK BGCs in different species of Monascus spp., and the results revealed that although LOV and MK were the same substance, the genes responsible for the synthesis of MK were much less than those for LOV synthesis, and the gene functions were quite different. The current results laid a foundation to explore the mechanism of MK produced by Monascus spp. and compare the synthesis of LOV and MK.