Lanosterol

About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.

Lanosterol to Ergosterol — Enzymology, Inhibition and Genetics

Abstract: The biosynthetic steps from lanosterol to ergosterol are of both pure and applied interest in terms of the biotransformations involved and in their inhibition by antifungal compounds. These antifungal compounds have application in medical (Saag and Dismukes 1988) and agricultural (Kuck and Scheinpflug 1986) contexts.

On the Concerted Ring Opening of Protonated Squalene Oxide and A-Ring Formation in the Biosynthesis of Lanosterol

Abstract: Density functional calculations were performed on a model system of squalene oxide to study the mechanism of the formation of ring A in the biosynthesis of lanosterol from squalene. When (2 Z )-6,7-epoxy-3,7-dimethyloct-2-ene was protonated, it was calculated to undergo a very facile ring opening of the oxirane in concert with the formation of the six-membered ring of the 4-(hydroxymethyl)-1,2,3,3-tetramethy1cyclohexyl cation. A study of the reaction pathway (IRC) indicates a very early transition structure in which the carbon- carbon double bond participates anchimerically in the ring-opening of the protonated oxirane. It is suggested that the primary role of the enzyme in this first step of the biosynthesis of lanosterol is protonation of the oxirane ring along with holding the substrate in the proper conformation for the concerted ring-closure to occur. The similarity between this mechanism and that recently proposed for concerted C-ring expansion and D-ring formation in the biosynthesis of lanosterol is discussed.

Cholesterol Biosynthesis Inhibitory Activities of Novel Triterpenoid Acids from Kadsura heteroclita and K. longipedunculata

Abstract: The effects of twelve novel triterpenoid acids isolated from the ethanolic extract of the stems of Kadsura heteroclita and A. longipedunculata, Chinese folk medicines, and three other novel triterpenoid acids semi-synthesized on cholesterol biosynthesis were examined. (24Z)-3-Oxo-lanosta-8,24-dien-26-oic acid (3-oxo-LA) was most active in depressing cholesterol biosynthesis from [2-14C] mevalonate in a 10,000 × g supernatant fraction of rat liver homogenate. It was suggested from the TLC analysis of radio-labeled products that these compounds inhibit the demethylation of lanosterol. Some triterpenoid acids including 3-oxo-LA also inhibited cholesterol biosynthesis from [1-14C]acetate in primary cultures of rat liver cells.

Engineering of cis-Element in Saccharomyces cerevisiae for Efficient Accumulation of Value-Added Compound Squalene via Downregulation of the Downstream Metabolic Flux.

Abstract: Transcriptional downregulation is widely used for metabolic flux control. Here, marO, a cis-element of Escherichia coli mar operator, was explored to engineer promoters of Saccharomyces cerevisiae for downregulation. First, the ADH1 promoter (PADH1) and its enhanced variant PUADH1 were engineered by insertion of marO into different sites, which resulted in decrease in both gfp5 transcription and GFP fluorescence intensity to various degrees. Then, marO was applied to engineer the native ERG1 and ERG11 promoters due to their importance for accumulation of value-added intermediates squalene and lanosterol. Elevated squalene content (4.9-fold) or lanosterol content (4.8-fold) and 91 or 28% decrease in ergosterol content resulted from the marO-engineered promoter PERG1(M5) or PERG11(M3), respectively, indicating the validity of the marO-engineered promoters in metabolic flux control. Furthermore, squalene production of 3.53 g/L from cane molasses, a cheap and bulk substrate, suggested the cost-effective and promising potential for squalene production.