Evidence for Uncultivable Microbes

It is estimated that only 1 % of the total microbial community has been cultured by standard isolation techniques. There is a growing conviction that this observation resulted from the selected media used, as well as incubation time and inoculum size. Additional stimulation factors for growth and sporulation (e.g. gamma-butyrolactones and indole-3-acetic acid) have been reported.41,42 This implies that the majority of microbial biodiversity still remains to be discovered and exploited. 

Until 1990, when Giovannoni and Ward applied 16S rRNA sequence analysis by extracting community DNA, microbiologists had to rely on plate counts of bacteria which could be cultured and isolated to obtain an idea of the number of bacteria in the sample.43,44 This new approach allowed the study of the remaining 99% of bacteria which could not be isolated by nutrient media and liquid enrichment. 

Genomic studies disclosed that many of those uncultivable microbes contain the potential to produce new secondary metabolites and there are a variety of routes to access this pool of novel natural products. For example, the community DNA gene clusters can be isolated and the genetic information for secondary metabolism expressed in heterologous hosts.45 47 A more rewarding approach may be to focus on improved cultivation methods.40,48 

Genomic studies have shown that the potential for producing secondary metabolites is not uniformly distributed across bacterial genera and species. Streptomyces coelicolor59 and S. avermitilis60 61 each possess more than 20 gene clusters responsible for the biosynthesis of secondary metabolites. The same 

The strong commitment of actinomycetes that devote 5-10% of their genetic capacity to secondary metabolism demonstrates why they are the unmatched leaders in the supply of novel antibiotics for over half a century. There is strong evidence that many hitherto undescribed actinomycetes taxa will be discovered among the uncultivable microbes. The successful laboratory cultivation of previously uncultured soil actinomycetes with a high degree of novelty demonstrates that even relatively simple isolation methods can still be extremely successful.40,48,50 51 

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