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environmental samples. Traditional microbiology studies cultivated clonal cultures. Metagenomics, in contrast, enables studies of organisms that are not easily cultured in a laboratory as well as studies of organisms in their natural environment. One of the first results to come from metagenomics was the realization that species identification efforts based on organisms that can be cultured had vastly underestimated the true level of biodiversity. While this conclusion is well accepted, identifying and exploiting the mass of information obtainable from these new life forms represents a major challenge and one that we are only now beginning to address.

Automated DNA synthesis has rapidly improved in fidelity, length, speed and cost. This enables the nucleotide information from sequencing and metagenomic efforts to be converted into a physical DNA sequence without the exchange of genetic or cellular material. So-called synthetic metagenomics refers to mining of databases for functional sequences, the “printing” of this information, and screening for function. This methodology will revolutionize enzyme/pathway/genetic circuit discovery, sequence-function mapping, and annotation of sequences. Novel bioinformatic methods will be needed to identify genes to be synthesized and to analyze the functional information.

A number of applications could require the forward programming of meta communities. Understanding the natural language and metabolic interdependencies of natural communities will aid in this process. Natural systems will yield more quorum sensing circuits that enable multiple channels by which cells can be programmed to communicate. Understanding the metabolic origins for symbiosis will enable multiple cells to be programmed to interact in a fermenter to achieve stable populations and predicable product titers.

Key Questions

  • How do we identify environmental sources for metagenomics analyses that are most likely to contain organisms capable of novel biosynthetic strategies that will be of immediate value to synthetic biology efforts?

  • How do we identify novel synthetic and signal transduction pathways from genomic information alone even when we are not able to culture a given organism? For example, comparative genomics, analysis of the environmental conditions in which organisms are found, metabolomics on polycultures.

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