A jadomycin is a

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 s ...

produced by ''

Streptomyces venezuelae ''Streptomyces venezuelae'' is a species of soil-dwelling Gram-positive bacterium of the genus ''Streptomyces''. ''S. venezuelae'' is filamentous. In its spore-bearing stage, hyphae perfuse both above ground as aerial hyphae and in the soi ...

'' ISP5230 (ATCC10712), the organism which is most well known for making the antibiotic

chloramphenicol Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by intravenous, injection into a vein, it is used to treat meningitis, pl ...

. The name jadomycin is applied to a family of related angucyclines which are distinguished by the E ring (usually an oxoazolone ring), which is derived from an amino acid. The amino acid incorporation which forms the E-ring is a chemical reaction, rather than enzymatic, an uncommon occurrence in biosynthesis. As such a number of jadomycins incorporating different amino acids have been discovered. Jadomycin A was the first compound of this family to be isolated and constitutes the angucylic backbone with L-isoleucine incorporated into the E-ring. A related analog, jadomycin B, is modified by glycosylation with a 2,6-dideoxy sugar, L-digitoxose. Jadomycins have cytotoxic and antibacterial properties.

Biosynthesis

The jadomycin biosynthetic gene cluster is well characterized. Jadomycin biosynthesis encompasses type II

polyketide synthase Polyketide synthases (PKSs) 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. The biosyntheses of polyketides share ...

(T2Pks) assembly to generate the angucycline component, and a dideoxy sugar pathway, to generate the sugar donor NDP-L-digitoxose. Studies have implicated JadG, an FAD-dependent

oxygenase An oxygenase is any enzyme that oxidizes a substrate by transferring the oxygen from molecular oxygen O2 (as in air) to it. The oxygenases form a class of oxidoreductases; their EC number is EC 1.13 or EC 1.14. Structure Most oxygenases contain ...

, in the ring cleavage required for incorporation of amino acids. JadS, the

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...

that transfers L-digitoxose, has been shown to be flexible with respect to the sugar donor.

Analogs based on E-ring modification

Jadomycin analogs have been obtained through culture of ''S. venezuelae'' in the presence of a single amino acid. The diversity of jadomycins includes those incorporating naturally occurring amino acids, non-proteinogenic amino acids, and synthetic amino acids with handles enabling further chemical modification.

References

{{Reflist Antibiotics Streptomyces Anthraquinone glycosides