Lovastatin-nonaketide synthase

Since we reported the enzymatic activity of SPS in 1995 as the first Diels-Alderase, two additional Diels-Alderases, lovastatin nonaketide synthase (LNKS) and macrophomate synthase (MPS), have been purified and characterized. Two of these catalyze intramolecular Diels-Alder reactions while the third catalyzes an intermolecular Diels-Alder reaction. We have recently reported the detailed reaction pathway ° ° of MPS and its catalytic mechanism based on the crystal structure. " In this section, we describe three natural Diels-Alderases and discuss the mechanism of their catalysis. 

J. C., Lovastatin nonaketide synthase catalyzes an intramolecular Diels-Alder reaction of substrate analogue, . Am. Chem. Soc., 2000,122, 11519-11520. 

Figure 10.5 Lovastatin biosynthetic pathway. LovB and LovC, a nonaketide synthase and enoyl reductase, respectively, generate the first stable intermediate, dihydromonacolin L. Monacolin L and Monacolin J are recognized pathway intermediates, however enzymes that catalyze these conversions have not been identified. LovF is a diketide synthase generating 2-methylbutyryl-CoA. This molecule is esterified to Monacolin J by LovD, generating Lovastatin.

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