Abstract
Monacolin K (MK), a secondary metabolite produced by Monascus spp. with the ability to inhibit cholesterol production, is structurally identical to lovastatin produced by Aspergillus terreus. In the lovastatin biosynthetic pathway, the polyketide synthase (PKS) encoded by lovB must work together with the enoyl reductase encoded by lovC to ensure lovastatin production. However, it is unclear whether mokA and mokE in the MK gene cluster of Monascus spp., both of which are highly homologous to lovB and lovC, respectively, also have the same functions for MK biosynthesis. In the current study, the high-yielding MK M. pilosus MS-1 was used as the research object, and it was found that the enoyl reductase domain of MokA may be non-functional due to the lack of amino acids at active sites, a function that may be compensated for by MokE in the MK synthesis pathway. Then, the mokE-deleted (ΔmokE), -complemented (ΔmokE::mokE), and -overexpressed (PgpdA-mokE) strains were constructed, and the results showed that ΔmokE did not produce MK, and ΔmokE::mokE restored MK synthesis, while the ability of PgpdA-mokE to produce MK was increased by 32.1% compared with the original strain MS-1. These results suggest that the MokA synthesized by Monascus spp. must be assisted by MokE to produce MK, just as lovastatin produced by A. terreus, which provides clues for further genetic engineering to improve the yield of MK in Monascus spp.