Origin of monacolin L from Aspergillus terreus cultures.
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.
Treiber
L R
LR
Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Reamer
R A
RA
Rooney
C S
CS
Ramjit
H G
HG
D000924:Anticholesteremic Agents / Q000378:metabolism*; D001230:Aspergillus / Q000378:metabolism*; D005285:Fermentation; D008148:Lovastatin / Q000096:biosynthesis; D009281:Naphthalenes / Q000096:biosynthesis*
D000924:Anticholesteremic Agents; D009281:Naphthalenes; C045375:monacolin L; D008148:Lovastatin