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C &EN's article on the first synthesis of platensimycin stated, "Platensimycin is the first antibiotic natural product with a new mechanism of action discovered in over 40 years" (C&EN, Oct. 9, page 12).
This statement is incorrect; two other natural compounds also discovered in the past 40 years, cerulenin and thiolactomycin, selectively inhibit the condensation enzymes FabF/B and FabH, leading to an inhibition of bacterial fatty acid biosynthesis. These enzymes are also inhibited by the newly discovered antibiotic platensimycin.
Although no drug targeting condensation enzymes is used clinically, it is worth noting that isoniazid, a well-known and clinically used antibiotic, inhibits fatty acid biosynthesis by blocking an enoyl-ACP reductase. Finally, triclosan, a chlorinated bisphenol, possesses broad-spectrum antibacterial action and is widely used in toothpastes, soaps, and plastics for hospital and consumer use. Triclosan is also an inhibitor of enoyl-ACP reductase.
So, there is no new mechanism of action for the new natural product platensimycin. Also, considering the unfavorable pharmacokinetic properties of platensimycin, it is hard to understand the excitement about the antibiotic properties of platensimycin.
Athanassios Giannis
Leipzig, Germany
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