A genomic screening approach to the structure-guided identification of drug candidates from natural sources.

The potential of actinomycetes to produce natural products has been exploited for decades. Recent genomic sequence analyses have revealed a previously unrecognized biosynthetic potential and diversity. In order to rationally exploit this potential, we have developed a sequence-guided genetic screening strategy.

Sulfation: a new biocombinatorial tool.

Considerable progress has been achieved in derivatization of glycopeptide antibiotics by using genetic engineering and in vitro enzymatic approaches. In this issue of Chemistry & Biology, the identification and application of a glycopeptide-specific sulfotransferase by Lamb et al. expands the tool box of biocombinatorial synthesis.

Mechanistic analysis of acyl transferase domain exchange in polyketide synthase modules.

Many polyketides are synthesized by a class of multifunctional enzymes called type I modular polyketide synthases (PKSs). Several reports have described the power of predictively altering polyketide structure by replacing individual PKS domains with homologues from other PKSs. For example, numerous erythromycin analogues have been generated by replacing individual methylmalonyl-specific acyl transferase (AT) domains of the 6-deoxyerythronolide B synthase (DEBS) with malonyl-, ethylmalonyl-, or methoxymalonyl-specific domains.