Publications

• Isolation and biosynthesis of 3 alpha-hydroxy-3,5-dihydromonacolin L.

  Nakamura T., Komagata D., Murakawa S., Sakai K., Endo A.

  3 alpha-Hydroxy-3,5-dihydromonacolin L acid (acid form), a new compound related to monacolin K (mevinolin), was isolated from the culture broth of a strain of Monascus ruber. The structure of the compound was determined by a combination of physical techniques. 4a,5-Dihydromonacolin L was converted ... >> More

  3 alpha-Hydroxy-3,5-dihydromonacolin L acid (acid form), a new compound related to monacolin K (mevinolin), was isolated from the culture broth of a strain of Monascus ruber. The structure of the compound was determined by a combination of physical techniques. 4a,5-Dihydromonacolin L was converted to 3 alpha-hydroxy-3,5-dihydromonacolin L by a cell-free extract of M. ruber in the presence of molecular oxygen. The results demonstrate that the former is the direct precursor in the biosynthesis of the latter. << Less

  J Antibiot (Tokyo) 43:1597-1600(1990) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Double oxidation of the cyclic nonaketide dihydromonacolin L to monacolin J by a single cytochrome P450 monooxygenase, LovA.

  Barriuso J., Nguyen D.T., Li J.W., Roberts J.N., MacNevin G., Chaytor J.L., Marcus S.L., Vederas J.C., Ro D.K.

  Lovastatin, a cyclic nonaketide from Aspergillus terreus, is a hypercholesterolemic agent and a precursor to simvastatin, a semi-synthetic cholesterol-lowering drug. The biosynthesis of the lovastatin backbone (dihydromonacolin L) and the final 2-methylbutyryl decoration have been fully characteri ... >> More

  Lovastatin, a cyclic nonaketide from Aspergillus terreus, is a hypercholesterolemic agent and a precursor to simvastatin, a semi-synthetic cholesterol-lowering drug. The biosynthesis of the lovastatin backbone (dihydromonacolin L) and the final 2-methylbutyryl decoration have been fully characterized. However, it remains unclear how two central reactions are catalyzed, namely, introduction of the 4a,5-double bond and hydroxylation at C-8. A cytochrome P450 gene, lovA, clustered with polyketide synthase lovB, has been a prime candidate for these reactions, but inability to obtain LovA recombinant enzyme has impeded detailed biochemical analyses. The synthetic codon optimization and/or N-terminal peptide replacement of lovA allowed the lovA expression in yeast (Saccharomyces cerevisiae). Both in vivo feeding and in vitro enzyme assays showed that LovA catalyzed the conversion of dihydromonacolin L acid to monacolin L acid and monacolin J acid, two proposed pathway intermediates in the biosynthesis of lovastatin. LovA was demonstrated to catalyze the regio- and stereo-specific hydroxylation of monacolin L acid to yield monacolin J acid. These results demonstrate that LovA is the single enzyme that performs both of the two elusive oxidative reactions in the lovastatin biosynthesis. << Less

  J. Am. Chem. Soc. 133:8078-8081(2011) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Origin of monacolin L from Aspergillus terreus cultures.

  Treiber L.R., Reamer R.A., Rooney C.S., Ramjit H.G.

  In freshly harvested Aspergillus terreus cultures grown for the production of lovastatin (formerly called mevinolin), no monacolin L could be detected. However, during the isolation of lovastatin, significant quantities of monacolin L appeared. It has been discovered that a new metabolite structur ... >> More

  In freshly harvested Aspergillus terreus cultures grown for the production of lovastatin (formerly called mevinolin), no monacolin L could be detected. However, during the isolation of lovastatin, significant quantities of monacolin L appeared. It has been discovered that a new metabolite structurally related to the members of the monacolin series is present. This metabolite is unstable and under mildly acidic conditions and elevated temperature, it converts to monacolin L. The subject metabolite is proven to be a hydroxylated derivative of dihydromonacolin L identified as 3 alpha-hydroxy-3,5-dihydromonacolin L. It seems that all monacolin L found later during various treatments of the broth and broth extracts is formed from that precursor via a dehydration reaction. The new metabolite was converted to its phenacyl ester, by means of extractive alkylation, for isolation and structure elucidation by chemical, chromatographic and spectroscopic methods. This ester, on standing, gradually formed the corresponding lactone. << Less

  J Antibiot (Tokyo) 42:30-36(1989) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.