**Conflict of interest**

*Extremophilic Microbes and Metabolites - Diversity, Bioprospecting and Biotechnological...*

Despite the individual technical limitations of both the approaches, it is regarded that the combined synergistic application of single-cell genomics and metagenomics can offer great opportunities, since the advantages offered by each of these techniques are complementary in nature. To highlight, it is underlined that one hand metagenomics is not known to suffer from any problem associated with chimera generation during strand displacement and genome amplification or separation of individual microbial cells from a complex heterogeneous mixture. On the other hand single-cell genomics overcomes the limitation of metagenomics by leading to a direct and unambiguous association of phylogeny and metabolic functions. Information obtained from SCGA can be effectively used to assign taxonomy to individual metagenome contigs with high accuracy [107, 112–114]. SCGA may also be used for retrieving complete genomes of candidate taxon from the metagenomic data. Similarly, the metagenomic reads can be mapped back to scaffolds for

closely related SAG and therefore significantly improve their annotation. The synergistic application of metagenomics and single cell genomics is regarded to have a unified and far reaching implication in harnessing the biotechnological potential of the extremophilic microbial diversity. As a matter of fact, extremophilic environments have already featured prominently in studies implementing both metagenomics and single-cell genomics studies. The most note-worthy set of studies were performed on acidophilic biofilms of Richmond Mine, California, USA, wherein initial metagenomic studies led to the identification of dominant microbial communities, while subsequent single cell genomics studies could identify even novel, low-abundance archaeal lineages that were later named as archaeal richmond mine acidophilic nanoorganisms (ARMAN) [115, 116]. The nanoorganisms have since been the matter of investigation throughout the world. In the same vein, the synergistic application of metagenomics and single cell genomics has led to identification of three previously uncultivated and uncharacterized halophilic phylotypes that represent the candidate phylum Nanohaloarchaeota from studies carried out on samples collected from halophilic Pola salterns, Alicante, Spain. Apart from the taxonomic and phylogenetic characterization of novel extremophiles, the synergistic application of metagenomics and single cell genomics also led to identification of their critical metabolic functions e.g. presence of

rhodopsin and genes for a photoheterotrophic lifestyle.

potential towards discovery of novel high value metabolites.

The advent of 'culture independent' approaches for characterization of microbial diversity and their dynamics has been the single most significant development in the field of microbiology in general and microbial ecology, microbial biotechnology in particular. It has also greatly accelerated the research pertaining to extremophilic microbial diversity. With use of present 'state of the art' technologies viz., metagenomics and single cell genomics, a number of vital discoveries have been made that would not have been possible without the use of these technologies. Thus, it could be proposed that although, considerable progress has been made, yet there is a lot of scope for better application of metagenomics and single-cell genomics approaches to not only access genomes for discovering novel taxonomic lineages of extremophilic microorganisms but also harness their genetic and metabolic

As an eventual future objective, the application of metagenomics and single cell genomics would be expected to complement the traditional cultivation approaches

**6.1 Combining single cell genomics and metagenomics**

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**7. Conclusion**

Authors declare 'no conflict of interest' with respect to publication of this book chapter.
