Department of Microbial Ecology, Centre for Ecological and Evolutionary Studies, University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands.
Appl Microbiol Biotechnol. 2012 Feb;93(3):1005-20. doi: 10.1007/s00253-011-3804-3. Epub 2011 Dec 22.
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.
功能宏基因组学是通过在异源宿主中表达微生物群落的总基因组来研究微生物群落的一门新兴生物技术。在过去的几年中，通过宏基因组学发现新型产品的可能性迅速发展。因此，宏基因组学被视为生物技术和制药行业资源的一种很有前途的挖掘策略。然而，尽管近年来在功能基因组学领域进行了创新工作，但基于功能的宏基因组学研究的产量仍然不足以产生对生物技术过程有价值的大量新产品。因此，与传统工作相比，需要采用一套新的策略来促进基因表达。这些新策略应该解决一个主要问题，即如何成功地在外源宿主中高效表达一组未知来源的未知基因。本文是对天然微生物群落的功能宏基因组筛选的意见性综述，重点是优化新产品的发现。它首先总结了功能宏基因组学目前的主要瓶颈，然后概述了一般的宏基因组评估策略，重点介绍了在宏基因组文库中筛选和选择靶基因所遇到的挑战。为了确定可能的筛选限制，还审查了实现最佳基因表达的策略，从转录水平到目标基因产物的分泌，考察了所有的分子事件。
