Lovastatin-nonaketide

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. 

Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis, J.L. Sorensen, K. Auclair, J. Kennedy, C.R. Hutchinson and J.C. Vederas, Org. Biomol. Chem., 2003,1, 50. 

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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