Historically, nature has provided the source for the majority of the drugs in use today. More than 20,000 microbial secondary metabolites have been described, but only a small percentage of these have been carried forward as natural product drugs. Natural products are in tough competition with large chemical libraries and with combinatorial chemistries. Hence, each step of a natural product program has to be more efficient than ever, starting from the collection of environmental samples and the selection of strains, to metabolic expression, genetic exploitation, sample preparation and chemical dereplication. This review will focus on approaches for diversifying microbial natural product strains and extract libraries, while decreasing genetic and chemical redundancy.

Aeromonas hydrophila ATCC 7966 grew anaerobically on glycerol with nitrate, fumarate, Fe(III), Co(III), or Se(VI) as the sole terminal electron acceptor, but did not ferment glycerol. Final cell yields were directly proportional to the amount of terminal electron acceptor provided. Twenty-four estuarine mesophilic aeromonads were isolated; all reduced nitrate, Fe(III), or Co(III), and five strains reduced Se(VI). Dissimilatory Fe(III) reduction by A. hydrophila may involve cytochromes. Difference spectra obtained with whole cells showed absorption maxima at wavelengths characteristic of c-type cytochromes (419, 522, and 553 nm). Hydrogen-reduced cytochromes within intact cells were oxidized by the addition of Fe(III) or nitrate. Studies with respiratory inhibitors yielded results consistent with a respiratory chain involving succinate (flavin-containing) dehydrogenase, quinones and cytochromes, and a single Fe(III) reductase. Neither anaerobic respiration nor dissimilatory metal reduction by members of the genus Aeromonas have been reported previously.

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Microbial consortia were enriched under sulfidogenic conditions using a common estuarine sediment inoculum with 2bromophenol or phenol as the sole the carbon source. Stable consortia were maintained over a 3-year period with repeated feeding and serial dilution into fresh medium. 2-Bromophenol was initially dehalogenated to phenol. Degradation of phenol was dependent on sulfate reduction and inhibited by molybdate, a specific inhibitor of sulfate reduction. Reductive dehalogenation of 2-bromophenol, however, was not dependent on, or inhibited by sulfate. The 2-bromophenol-and phenoldegrading sulfidogenic consortia were characterized using 16S rRNA restriction fragment length polymorphism analysis and unique clones were sequenced. Terminal restriction fragment length polymorphism of all individual clones and both microbial consortia indicated that all 16S rRNA types present in the consortia were cloned and characterized. Four phylotypes were identified from the 2-bromophenol-utilizing consortium which based upon their 16S rRNA sequences clustered into three major groups: one sequence was related to the O-subgroup of the Proteobacteria, two clones clustered within the sulfatereducers (N-subgroup of Proteobacteria), the fourth phylotype was divergent from previously described bacteria and was most closely related to the genus Planctomycetes. None of the clones from the 2-bromophenol-degrading consortium are close to previously described aryl-dehalogenating bacteria which predominantly comprise the genera Desulfitobacterium and Desulfomonile. In contrast, the phenol-degrading consortium yielded only two clonal types. One was placed within the Osub-division of the Proteobacteria with Thiomicrospira denitrificans as its closest neighbor. The other clone was closest to the genus Cytophaga with Anaeroflexus maritimus as its closest neighbor. z

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