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Tetrahydroxanthones are 
The ''nsr cluster'' is a 
The biosynthesis of tetrahydroxanthones begins with the synthesis of the 
natural product
A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical sy ...
s formally derived by partial reduction of xanthone
Xanthone is an organic compound with the molecular formula O 6H4sub>2CO. It is a white solid.
In 1939, xanthone was introduced as an insecticide and it currently finds uses as ovicide for codling moth eggs and as a larvicide. Xanthone is also ...
. They are produced by various fungi
A fungus (plural, : fungi or funguses) is any member of the group of Eukaryote, eukaryotic organisms that includes microorganisms such as yeasts and Mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified ...
, bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
, and plant
Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...
s. Some are precursors to larger xanthone natural products. One example is neosartorin, composed of 5-acetylblennolide A and blennolide C, exhibits antibacterial
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
activity against Gram-positive bacteria
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.
Gram-positive bact ...
, notably including ''Staphylococcus aureus
''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posit ...
''.
Chrysophanol
Chrysophanol, also known as chrysophanic acid, is a fungal isolate and a natural anthraquinone. It is a C-3 methyl substituted chrysazin of the trihydroxyanthraquinone family.
Chrysophanol (other names; 1,8-dihydroxy-3-methyl-anthraquinone and ...
is the common intermediate to most if not all tetrahydroxanthones.
The ''nsr cluster'' is a polyketide synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
gene responsible for the biosynthesis of neosartorin in ''A. novofumigatus''. The enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
''NsrQ'' features a catalytic
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycl ...
glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
residue in the active site which protonates the enol produced by ''NsrK'', leading to dearomatization A dearomatization reaction is an organic reaction which involves arenes as reactants and in which the reaction products have permanently lost their aromaticity. This reaction type is of some importance in synthetic organic chemistry for the organic ...
.
The biosynthesis of tetrahydroxanthones begins with the synthesis of the anthraquinone
Anthraquinone, also called anthracenedione or dioxoanthracene, is an aromatic organic compound with formula . Isomers include various quinone derivatives. The term anthraquinone however refers to the isomer, 9,10-anthraquinone (IUPAC: 9,10-dioxoan ...
chrysophanol (see figure). Once the final reduction and dehydration
In physiology, dehydration is a lack of total body water, with an accompanying disruption of metabolic processes. It occurs when free water loss exceeds free water intake, usually due to exercise, disease, or high environmental temperature. Mi ...
events take place (''NsrJ'' and ''NsrI''), chrysophanol is accepted into monooxygenase
Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation ...
''NsrF''. A ring opening occurs upon the addition
Addition (usually signified by the plus symbol ) is one of the four basic operations of arithmetic, the other three being subtraction, multiplication and division. The addition of two whole numbers results in the total amount or ''sum'' of ...
of water to the ''NsrF'' product 8 to give 9. ''NsrG'', a methyltransferase
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Ros ...
, then converts the carboxylic acid
In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...
into an ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
, giving 10 as the product. ''NsrK'', a flavin-dependent monooxygenase, the installs an alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
''ortho''- to the ester and methyl group
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in ma ...
s, breaking the aromaticity
In chemistry, aromaticity is a chemical property of cyclic (ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to sat ...
of the compound. ''NsrQ,'' an NADPH dependent ketoreductase, then isomer
In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers.
...
izes the methyl group to form 12 and 14. The two isomers are then acted upon by either ''NsrO'' and ''CPUR_05418'' or just ''NsrO'' to give (-)-blennolide B and blennolide A. Further transformation of blennolide A by ''NsrL'' yields the precursor natural product 5-actelyblennolide A.
References
{{Reflist Xanthones