6ad3

Structural highlights

Function

MOKA_MONPI Nonaketide synthase; part of the gene cluster that mediates the biosynthesis of monakolin K, also known as lovastatin, and which acts as a potent competitive inhibitor of HMG-CoA reductase (PubMed:18578535). Monakolin K biosynthesis is performed in two stages (PubMed:19693441). The first stage is catalyzed by the nonaketide synthase mokA, which belongs to type I polyketide synthases and catalyzes the iterative nine-step formation of the polyketide (PubMed:18578535, PubMed:19693441). This PKS stage is completed by the action of dehydrogenase mokE, which catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the mokA-mediated biosynthesis of the nonaketide chain and leads to dihydromonacolin L (PubMed:19693441). Covalently bound dihydromonacolin L is released from mokA by the mokD esterase (By similarity). Conversion of dihydromonacolin L into monacolin L and then monacolin J is subsequently performed with the participation of molecular oxygen and P450 monoogygenase mokC (PubMed:19693441). Finally, mokF performs the conversion of monacoline J to monacoline K through the addition of the side-chain diketide moiety (2R)-2-methylbutanoate produced by the diketide synthase mokB (PubMed:19693441).[UniProtKB:Q0C8M2][UniProtKB:Q9Y8A5]^{[1] [2]}

References

1. ↑ Chen YP, Tseng CP, Liaw LL, Wang CL, Chen IC, Wu WJ, Wu MD, Yuan GF. Cloning and characterization of monacolin K biosynthetic gene cluster from Monascus pilosus. J Agric Food Chem. 2008 Jul 23;56(14):5639-46. doi: 10.1021/jf800595k. Epub 2008 , Jun 26. PMID:18578535 doi:http://dx.doi.org/10.1021/jf800595k
2. ↑ Sakai K, Kinoshita H, Nihira T. Identification of mokB involved in monacolin K biosynthesis in Monascus pilosus. Biotechnol Lett. 2009 Dec;31(12):1911-6. doi: 10.1007/s10529-009-0093-3. Epub, 2009 Aug 20. PMID:19693441 doi:http://dx.doi.org/10.1007/s10529-009-0093-3