Biodiversity for biocatalysis: A review of the α/β-hydrolase fold superfamily of esterases-lipases discovered in metagenomes

Review Article.Natural biodiversity undoubtedly inspires biocatalysis research and innovation. Biotransformations of interest also inspire the search for appropriate biocatalysts in nature. Indeed, natural genetic resources have been found to support the hydrolysis and synthesis of not only common but also unusual synthetic scaffolds. The emerging tool of metagenomics has the advantage of allowing straightforward identification of activity directly applicable as biocatalysis. However, new enzymes must not only have outstanding properties in terms of performance but also other properties superior to those of well-established commercial preparations in order to successfully replace the latter. Esterases (EST) and lipases (LIP) from the α/β-hydrolase fold superfamily are among the enzymes primarily used in biocatalysis. Accordingly, they have been extensively examined with metagenomics. Here we provided an updated (October 2015) overview of sequence and functional data sets of 288 EST–LIP enzymes with validated functions that have been isolated in metagenomes and (mostly partially) characterized. Through sequence, biochemical, and reactivity analyses, we attempted to understand the phenomenon of variability and versatility within this group of enzymes and to implement this knowledge to identify sequences encoding EST–LIP which may be useful for biocatalysis. We found that the diversity of described EST–LIP polypeptides was not dominated by a particular type of protein or highly similar clusters of proteins but rather by diverse nonredundant sequences. Purified EST–LIP exhibited a wide temperature activity range of 10–85 °C, although a preferred bias for a mesophilic temperature range (35–40 °C) was observed. At least 60% of the total characterized metagenomics-derived EST–LIP showed outstanding properties in terms of stability (solvent tolerance) and reactivity (selectivity and substrate profile), which are the features of interest in biocatalysis. We hope that, in the future, the search for and utilization of sequences similar to those already encoded and characterized EST–LIP enzymes from metagenomes may be of interest for promoting unresolved biotransformations in the chemical industry. Some examples are discussed in this review.The authors gratefully acknowledge the financial support provided by the European Community project MAMBA (FP7-KBBE-2008-226977), MAGIC-PAH (FP7-KBBE-2009-245226), ULIXES (FP7-KBBE-2010-266473), MicroB3 (FP7-OCEAN.2011-2-287589), KILL-SPILL (FP7-KBBE-2012-312139) and Royal Society UK-Russia Exchange Grant (IE130218). We thank EU Horizon 2020 Program for the support of the Project INMARE H2020-BG-2014-2634486. This work was further funded by grants BIO2011-25012,PCIN-2014-107 and BIO2014-54494-R from the Spanish Ministry of Economy and Competitiveness. The present investigation was funded by the Spanish Ministry of Economy and Competitiveness, the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the German Federal Ministry of Education and Research (BMBF) within the ERA NET-IB2 program, grant number ERA-IB-14-030. The authors gratefully acknowledge the financial support provided by the European Regional Development Fund (ERDF).Peer reviewe