Erythromycin commercial products

The commercial production of penicillin and other antibiotics are the most dramatic in industrial microbiology. The annual production of bulk penicillin is about 33 thousand metric tonnes with annual sales market of more than US 400 million.8 The worldwide bulk sales of the four most important groups of antibiotics, penicillins, cephalosporins, tetracyclines and erythromycin, are US 4.2 billion per annum.10... 

The erythromycins (Figure 3.65) are macrolide antibiotics produced by cultures of Saccharopolyspora erythraea (formerly Streptomyces erythreus). The commercial product... 

The commercial product is erythromycin A. which differs from its bio.syntlietic precursor, erythromycin B, in having a hydroxyl group at the 12 position of the aglycone. The chemical structure of erythromycin A was reported by Wiley et al. in I9.S7 and its stereochemistry by Celmer in 1965. An elegant synthesis of erythronolidc A, the aglycone pre.sent in erythromycin A. wa.s described by Corey and associates. ... 

Over the years it has been interesting to note that many compounded products eventually become commercially available products. Recent examples might include fentanyl lozenges, minoxidil topical solution, nystatin lozenges, clindamycin topical solution, tetracaine-adrenalin-cocaine (TAG) solution, dihydroergotamine mesylate nasal spray, buprenorphine nasal spray, buffered hypertonic saline solution, and erythromycin topical solution as well as numerous other dermatological and pediatric oral liquids and some... 

Erythromycin base is reported to exist in a number of structural forms, including an anhydrate, a dihydrate, and an amorphous form [109, 110]. The commercially available product appears to be a partially crystalline material, containing a significant amount of amor-... 

Although recent advances in total synthesis are now approaching feasibility for structure-activity studies, chemical modification of erythromycin is still the most practical route for the synthesis of derivatives, since the starting material is readily available from fermentation sources. All of the commercially available derivatives of erythromycin as well as those in various stages of development are semi-synthetic products. The rationale for synthesis of many of these derivatives has been largely influenced by the mechanism of decomposition of erythromycin. 

An instance of pathway manipulation with potentially high commercial significance was the production of epirubidn in S.peucetius [13]. The (4S)-TDP-4-keto-6-deoxyhexose reductase gene, dnmV, was disrupted by insertional inactivation, and the gene for a homologous reductase from erythromycin (EryBIV) or avermectin (AvrE) biosynthesis, with different product stereochemistry (4R), was introduced to the production strain (Scheme 9). 

Polyketides are an extraordinarily valuable class of natural products, numbering over 10,000 compounds. Commercially important polyketides include antibiotics (erythromycin A, tetracycline) and immunosuppressants (rapamycin), as well as anticancer (doxorubicin), antifungal (amphotericin B), and cholesterol-lowering (lovastatin) agents (Figure 25.15). It has been estimated that the sales of these and other polyketide pharmaceuticals total more than 15 billion per year. 

APIs are sold in bulk, typically as powder in a drum. Global demand for very common APIs such as paracetamol, erythromycin or ibuprofen is as high as 60,000 tons per year. Volume demand for most APIs is in the range of 10 to 500 tons per year. Economies of scale are important for both API and FPP production. A manufacturing facility must be operating at close to its full capacity to maximize operational efficiency. Companies that manufacture both APIs and FPPs possess a competitive market advantage because there is one less commercial transaction where profit is taken in the value chain. 

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