Oxytetracycline

Oxytetracycline therefore stops the spread of the infection, and the remaining bacteria are killed by the immune system or eventually die.

Oxytetracycline may be used to treat other rarer infections, such as those caused by a group of microorganisms called rickettsiae (e.g., Rocky Mountain spotted fever).

Oxytetracycline is used to treat infections of the respiratory and urinary tracts, skin, ear, eye and gonorrhoea, although its use for such purposes has declined in recent years due to large increases in bacterial resistance to this class of drugs.

Oxytetracycline is especially valuable in treating nonspecific urethritis, Lyme disease, brucellosis, cholera, typhus, tularaemia, and infections caused by Chlamydia, Mycoplasma, and Rickettsia.

Occasionally, oxytetracycline is given by intramuscular injection or topically in the form of creams, ophthalmic ointments, or eye drops.

It sometimes causes nasal cavities to erode; because of this, tetracyclines should not be used to treat pregnant or lactating women and children under age twelve except in certain conditions where it has been approved by a specialist because there are no obvious substitutes.

It was first found near Pfizer laboratories in a soil sample yielding the actinomycete Streptomyces rimosus by Finlay et al.

The biosynthesis of oxytetracycline begins with the utilization of PKS enzymes ketosynthase (KS), the chain length factor (CLF), the acyl carrier protein (ACP), and an acyltransferase (encoded as OxyA, OxyB, OxyC and OxyP in the oxytetracycline gene cluster)[7] to catalyze the extension of the malonamyl-CoA starting unit with eight malonyl-CoA extender units.

[8] Thus, minimal PKSs form a completed amidated polyketide backbone without any additional post-synthase tailoring enzymes (Figure 1).

Following the formation of the linear tetracyclic skeleton, four successive cyclization reactions must occur in a regioselective manner to produce the aromatic natural product known as pretetramid, a common precursor to both oxytetracycline and other tetracycline antibiotics.

After the formation of anhydrotetracycline, ATC monooxygenase (OxyS) oxidizes the C-6 position in an enantioselective manner in the presence of the cofactor NADPH and atmospheric oxygen to produce 5a,11a-dehydrotetracycline.

[13] This research helps producers understand the effects of oxytetracycline in animal feed on the environment, bacteria, and antimicrobial resistance.

Figure 1. The oxytetracycline gene cluster extends the malonamyl-CoA starting unit with 8 × malonyl-CoA to form an amidated polyketide backbone en route to Oxytetracycline.
Figure 2. Biosynthesis of oxytetracycline starting from the intermediate anhydrotetracycline. Bottom: Proposed arrow-pushing mechanism of oxytetracycline formation.