The metabolic origin of the sulfur atom in the naturally occurring antibiotic lincomycin A has been obscure — until now. The biosynthetic steps involved reveal surprising roles for two sulfur-containing metabolites. See Letter p.115 The biosynthetic origins of sulfur atoms found in natural products — or secondary metabolites — are not well understood. Mycothiol (MSH) is a cysteinyl pseudo-disaccharide found in Gram-positive actinobacteria, and the conjugation of this thiol-containing compound to electrophilic toxins facilitates their excretion from the bacterial cell. Actinomycetes also produce another thiol, ergothioneine (EGT), a histidine betaine derivative of unknown function. In this paper, the authors showed that MSH and EGT have important roles in the biosynthesis of lincomycin A, a sulfur-containing antibiotic that is used to treat severe Gram-positive bacterial infections in people who cannot receive penicillin antibiotics.
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