58889-19-3Relevant academic research and scientific papers
Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis at the lovA and lovC genes
Sorensen, John L.,Auclair, Karine,Kennedy, Jonathan,Hutchinson, C. Richard,Vederas, John C.
, p. 50 - 59 (2007/10/03)
Two mutants of Aspergillus terreus with either the lovC or lovA genes disrupted were examined for their ability to transform nonaketides into lovastatin 1, a cholesterol-lowering drug. The lovC disruptant was able to efficiently convert dihydromonacolin L 5 or monacolin J 9 into 1, and could also transform desmethylmonacolin J 15 into compactin 3. In contrast, the lovA mutant has an unexpectedly active β-oxidation system and gives only small amounts of 1 upon addition of the immediate precursor 9, with most of the added nonaketide being degraded to heptaketide 22. Similarly, the lovA mutant does not accumulate the polyketide synthase product 5 and rapidly degrades any 5 added as a precursor via two cycles of β-oxidation and hydroxylation at C-6 to give 20. The possible involvement of epoxides 21a and 21b in the biosynthesis of 1 was also examined, but their instability in fermentation media and fungal cells will require purified enzymes to establish their role.
Conversion of cyclic nonaketides to lovastatin and compactin by a lovC deficient mutant of Aspergillus terreus
Auclair, Karine,Kennedy, Jonathan,Hutchinson, C. Richard,Vederas, John C.
, p. 1527 - 1531 (2007/10/03)
Investigation of the post-PKS biosynthetic steps to the cholesterol-lowering agent lovastatin (1) using an Aspergillus terreus strain with a disrupted lovC gene, which is essential for formation of 4a,5-dihydromonacolin L (3), shows that 7 and 3 are precursors to 1, and demonstrates that lovastatin diketide synthase (lovF protein) does not require lovC.
Total Syntheses of ML-236A and Compactin by Combining the Lactonic (Silyl) Enolate Rearrangement and Aldehyde-Diene Cyclocondensation Technologies
Danishefsky, Samuel J.,Simoneau, Bruno
, p. 2599 - 2604 (2007/10/02)
The sequence of a lactonic Claisen rearrangement and a Lewis acid catalyzed cyclocondensation of an aldehyde with an appropriate diene affords a new route to the title series.
Purification and Properties of Carboxylesterase from Emericella unguis that Catalyzes the Conversion of ML-236B (Compactin) to ML-236A
Murakawa, Shigeo,Nakamura, Takeshi,Komagata, Daisuke,Sunagawa, Emi,Endo, Akira
, p. 1879 - 1884 (2007/10/02)
A carboxylesterase that hydrolyzes ML-236B (compactin) to ML-236A (ML-236B esterase) has been extracted from mycelia of Emericella unguis and purified to homogeneity by successive ammonium sulfate fractionation, chromatography on DEAE-cellulose, gel filtration on Sephadex G-75 and preparative gel electrophoresis.The molecular weight of the purified enzyme was found to be ca. 40,000 and its optimum pH to be around 8.Of the p-nitrophenylesters with different C-chain lengths tested, p-nitrophenylbutyrate (C4) was the best substrate for the enzyme.Since ML-236B is an α-methylbutyryl ester of Ml-236A, the data suggested that the E. unguis esterase is highly specific for the C4-chain length. β-Naphtylacetate, tributyrin, olive oil and casein were not hydrolyzed.The ML-236B esterase was sensitive to N-ethylmaleimide and the organophosphate, DDVP, but resistant to eserine (carbamate), NaF and EDTA.
