Rapamycin, polyketide derivatives

Many important therapeutics, in use in clinics today, are biosynthesized by the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) paradigm. For example, many of the antibiotics (penicillin, cephalosporin, vancomycin, erythromycin, etc.), immunosuppressors (cyclosporine, rapamycin), antiviral agents (luzopeptin A), antitumor agents (bleomycin), and toxins (thaxtomin) are NRPS and PKS derived.20-22 Figure 1 displays a small selection of natural products that are NRPS and PKS derived and illustrates the diversity of molecular structures generated by these biosynthetic paradigms. 

D-alanine residue. Other polyketides which contain such an arrangement are the trienomycins [99], while similar CHC chain terminating (synthase starter) units are found in a branch of asukamycin [96], and in the eo-cyclohexyl fatty acids of certain thermophilic bacteria [100] substituted CHCs are also found as PKS starter units in the rapamycin family of polyketides (see Sect. 8). The cyclohexyl moieties of these compounds have been demonstrated to derive from the shiki-mate pathway. 

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