Abstract
For half a century, natural products from microorganisms have been the main source of medicines for treating infectious disease. The most important chemical class of these antibiotics, apart from the penicillins, is the polyketides. They are made by the stepwise building of long carbon chains, two atoms at a time, by multifunctional enzymes that determine the chain length, oxidation state, and pattern of branching, cyclisation, and stereochemistry of the molecules in a combinatorial fashion to produce an enormous variety of structures. Recent elucidation of the genetic ‘programming’ of the enzymes has opened a new field of drug discovery based on rationally engineering the enzymes to produce ‘unnatural natural products’ with novel properties.
Highlights
For half a century, natural products from microorganisms have been the main source of medicines for treating infectious disease
While a fungus makes penicillin, semisynthetic derivatives of which have been a mainstay of antibacterial therapy for decades, most natural antibacterial antibiotics come from a group of soildwelling, filamentous bacteria called the actinomycetes, of which Streptomyces is the best-known genus
While many different chemical classes are represented amongst actinomycete antibiotics, one class accounts for an extraordinary proportion of the important compounds, including all those mentioned above
Summary
Natural products from microorganisms have been the main source of medicines for treating infectious disease. While a fungus makes penicillin, semisynthetic derivatives of which have been a mainstay of antibacterial therapy for decades, most natural antibacterial antibiotics come from a group of soildwelling, filamentous bacteria called the actinomycetes, of which Streptomyces is the best-known genus. These organisms make an amazing array of so-called secondary metabolites that have evolved to give their producers a PLoS Biology | http://biology.plosjournals.org competitive advantage in the complex soil environment, where they are exposed to stresses of all kinds (Challis and Hopwood 2003). How do PKSs work and how can we make new ones?
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