The Role of Enoyl Reductase in the Monacolin K Biosynthesis Pathway in spp.

Monacolin K (MK), a secondary metabolite produced by spp. with the ability to inhibit cholesterol production, is structurally identical to lovastatin produced by In the lovastatin biosynthetic pathway, the polyketide synthase (PKS) encoded by must work together with the enoyl reductase encoded by to ensure lovastatin production. However, it is unclear whether and in the MK gene cluster of spp., both of which are highly homologous to and , respectively, also have the same functions for MK biosynthesis. In the current study, the high-yielding MK 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 -deleted (Δ), -complemented (Δ), and -overexpressed () strains were constructed, and the results showed that Δ did not produce MK, and Δ restored MK synthesis, while the ability of to produce MK was increased by 32.1% compared with the original strain MS-1. These results suggest that the MokA synthesized by spp. must be assisted by MokE to produce MK, just as lovastatin produced by , which provides clues for further genetic engineering to improve the yield of MK in spp.