Zaragozic acids are a family of natural product

Natural product

A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...

s produced by fungi

Fungus

A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

. The first characterized zaragozic acids, A, B, and C were isolated from an unidentified sterile fungal

Sterile fungi

The sterile fungi, or mycelia sterilia are a group of fungi that do not produce any known spores, either sexual or asexual. This is considered a form group, not a taxonomic division, and is used as a matter of convenience. Because these fungi do not produce spores, it is impossible to use...

 culture

Cell culture

Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

, S. intermedia, and L. elatius

Leptodontidium elatius var. elatius

Leptodontidium elatius var. elatius is a slow growing pathanogenic ascomycete fungus responsible for Sooty Blotch disease.-External links:* *...

, respectively. just outside of the European city Zaragoza

Zaragoza

Zaragoza , also called Saragossa in English, is the capital city of the Zaragoza Province and of the autonomous community of Aragon, Spain...

, Spain

Spain

Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...

 on the Jalón

Jalón (river)

The river Jalón is located in the northeast of Spain, and is one of the principal tributaries of the Ebro. It has a length of and drains a watershed of . The flow rate in Calatayud is , but is highly irregular due to the great range of Mediterranean rainfall patterns.The course of the river forms...

 river. This family of natural products possesses a unique 4,8-dioxabicyclo[3.2.1]octane core, and vary in their 1-alkyl and their 6-acyl side chains.

Uses

Zaragozic acids are potent inhibitor

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

s of S. cervisiae

Saccharomyces cerevisiae

Saccharomyces cerevisiae is a species of yeast. It is perhaps the most useful yeast, having been instrumental to baking and brewing since ancient times. It is believed that it was originally isolated from the skin of grapes...

, fungal and mammalian squalene synthase

Farnesyl-diphosphate farnesyltransferase

Farnesyl-diphosphate farnesyltransferase is an enzyme that converts two units of farnesyl pyrophosphate into squalene....

 and therefore inhibitors of sterol synthesis. Squalene synthase is the first committed enzyme in sterol synthesis, catalyzing the reductive condensation of farnesyl pyrophosphate to form squalene. As a squalene synthase inhibitor, zaragozic acid produces lower plasma cholesterol

Cholesterol

Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 levels in primates. Treatment of rats with zaragozic acid A caused an increase in hepatic low density lipoprotein (LDL) receptor

LDL receptor

The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...

 mRNA levels.

Zaragozic acids also mildly inhibit Ras farnesyl-protein transferase.

Zaragozic acid D and D2 have been isolated from the keratinophilic fungus Amauroascus niger.

Biosynthesis

The core biosynthetic route is via an polyketide synthase

Polyketide synthase

Polyketide synthases are a family of multi-domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages...

pathway from 10 acetates,
4 methyls of methionines, 1 succinate, and 1 benzoic acid.