Streptomyces cattleya reactions

So far only a few dozen organofluorine compounds have been isolated from living organisms, for example fluoroacetic acid, 4-fluorothreonine and rw-fluoro-oleic acid [244-246], The reason that nature has not invested in fluorine chemistry could be a combination of low availability of water-dissolved fluoride in the environment due to its tendency to form insoluble fluoride salts, and the low reactivity of water-solvated fluoride ion. However, in 2002, O Hagan and collaborators [247] published the discovery of a biochemical fluorination reaction in a bacterial protein extract from Streptomyces cattleya converting S-adenosyl-L-methionine (SAM) to 5 -fluoro-5 deoxyadenosine (5 -FDA). The same protein extract contained also the necessary enzymatic activity to convert 5 -FDA into fluoroacetic acid. In 2004, the same authors published the crystal structure of the enzyme and demonstrated a nucleophilic mechanism of fluorination [248,249]. 

C.D. Cadicamo, J. Courtieu, H. Deng, A. Meddour, D. O Hagan, Enzymatic fluorina-tion in Streptomyces cattleya takes place with an inversion of configuration consistent with an Sn2 reaction mechanism, ChemBioChem 5 (2004) 685-690. 

Scheme 1. The reactions of the Streptomyces cattleya cell-free extract incubation of ATP 7 and fluoride ion, illustrating the formation of 5 -FDA 5, 5 -FDI 6 and FAc 1. L-methionine is recycled between SAM synthetase and the fluorinase [7].

Cadicamo CD, Courtieu J, Deng H, Meddour A, O Hagan D (2004) Enzymatic Fluorination in Streptomyces cattleya Takes Place with an Inversion of Configuration Consistent with an Sn2 Reaction Mechanism. ChemBioChem 5 685... 

Thienamycin, the first of the carbapenems, was isolated from Streptomyces cattleya. Because of its extremely intense and broad-spectrum antimicrobial activity as well as its ability to inactivate (3-lactamases, it combines in one molecule the functional features of the best of the (3-lactam antibiotics as well as the (3-lactamase inhibitors. It differs structurally in several important respects from the penicillins and cephalosporins. The sulfur atom is not part of the 5-membered ring but, rather, has been replaced by a methylene moiety at that position. Carbon is roughly half the molecular size of sulfur. Consequently, the carbapenem ring system is highly strained and very susceptible to reactions cleaving the (3-lactam bond. The sulfur atom is now attached to C-3 as part of a functionalized side chain. 

Fluorination of organic compounds using fluoride ion can be catalyzed by enzymes (Fig. 10.38). For example, fluorinase from Streptomyces cattleya catalyzes C—F bond formation in the reaction of S-adenosyl-L-methionine with fluoride to yield 5 -fluoro-5 -deoxyadenosine. " Although their substrate scope is hmited at present, these kinds of enzymes may come to play an important role for fluorination in the future due to the ease, mildness and safety of the reaction conditions and the use of fluoride as fluorine source. 

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