The great screen anomaly—a new frontier in product discovery through functional metagenomics

Functional metagenomics, the study of the collective genome of a microbial community by expressing it in a foreign host, is an emerging field in biotechnology. Over the past years, the possibility of novel product discovery through metagenomics has developed rapidly. Thus, metagenomics has been heralded as a promising mining strategy of resources for the biotechnological and pharmaceutical industry. However, in spite of innovative work in the field of functional genomics in recent years, yields from function-based metagenomics studies still fall short of producing significant amounts of new products that are valuable for biotechnological processes. Thus, a new set of strategies is required with respect to fostering gene expression in comparison to the traditional work. These new strategies should address a major issue, that is, how to successfully express a set of unknown genes of unknown origin in a foreign host in high throughput. This article is an opinionating review of functional metagenomic screening of natural microbial communities, with a focus on the optimization of new product discovery. It first summarizes current major bottlenecks in functional metagenomics and then provides an overview of the general metagenomic assessment strategies, with a focus on the challenges that are met in the screening for, and selection of, target genes in metagenomic libraries. To identify possible screening limitations, strategies to achieve optimal gene expression are reviewed, examining the molecular events all the way from the transcription level through to the secretion of the target gene product

Exploring the bioactive landscape of the gut microbiota to identify metabolites underpinning human health

The healthy human gut is colonised by a diverse microbial community (gut microbiota) that provides a variety of ecological and metabolic functions relevant to host health and well-being. Our early understanding and appreciation of the functional capacity of the microbiota was primarily informed by culture-dependent analyses. However, it is now known that the vast majority of gut microbes are resistant to cultivation and remain unrepresented by cultured isolates. Consequently, much of our current awareness of the true biological potential inherent to these communities has been provided by culture-independent (meta)genomic approaches which have revealed that the genetic potential of the gut microbiota is as much as 150 times greater than that of the human genome itself. Despite these advances it is now increasingly accepted that efforts to dissect the functionalities encoded in the human microbiome have not kept pace with DNA sequencing based technologies. For instance, the microbiome encodes a plethora of bioactive peptides and metabolites that affect host health, however, the function(s), mechanism(s) of action and the genetic and regulatory networks underpinning these bioactives remain largely cryptic. Here, we explore the NF-?B suppressive bioactive landscape of the gut microbiota-in particular, we provide an overview of our current understanding of the gut microbiota and propose the integration of new culture-dependent approaches with improved screening, metabolomic and genetic strategies offers new opportunities to identify novel bioactives, and elucidate the relationship between the gut microbiota associated metabolome and host health