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Ene-Reductases in Pharmaceutical Chemistry
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
In the 1960s, fosfomycin (originally phosphonomycin, trade names Monurol and Monuril) was isolated by screening fermentation broths of Streptomyces fradiae within a collaborative project between Merck and the Spanish “Compañía Española de Penicilina y Antibióticos” (CEPA) (Hendlin et al., 1969). The compound exhibited broad antibacterial activity against Gram-positive as well as Gram-negative pathogens, and for more than 20 years, it has been used as an oral treatment for urinary tract infections (Silver, 2017). Due to its unique mode of action—inhibition of murein biosynthesis through irreversible interaction with enzyme MurA—fosfomycin makes cross-resistance uncommon and allows for synergies with other antibiotics (Falagas et al., 2016). In an era of antibiotic resistance and limited new treatment options, fosfomycin is of interest against multidrug-resistant (MDR) and extensively drug-resistant (XDR) nosocomial (hospital-acquired) infections, for which limited treatment options are available. Fosmidomycin, on the other hand, inhibits DXP reductoisomerase, a key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis, and thus is considered for treatment of malaria in combination with for example clindamycin (Ruangweerayut et al., 2008).
The circulation of penicillin in Spain: health, wealth and authority
Published in Annals of Science, 2019
Santesmases also provides an assessment of the screening programme of new antibiotics carried out at CEPA, a company which had acquired technology and knowledge from Merck. The project was carried out in close contact with the Rahway firm. Although the screening programme was not an advanced project for Merck, it resulted in the synthesis of a new antibiotic, fosfomycin, and it eased the circulation of knowledge and researchers between Spain and the USA. In Santesmases's view the CEPA screening programme was an instance of the transfer of industrial research organization to the laboratory. This is another interesting point that the author could have developed by comparing the CEPA case with other contemporary networks of innovation in Spain.