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Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts.

ABSTRACT: In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries as a valuable and promising source of novel bioactive compounds. Marine biodiscovery programmes have begun to reveal the extent of novel compounds encoded within the enormous bacterial richness and diversity of the marine ecosystem. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, underscores the potential of the marine environment to deliver on functionally novel biocatalytic activities. With the growing need for green alternatives to industrial processes, and the unique transformations which nature is capable of performing, marine biocatalysts have the potential to markedly improve current industrial pipelines. Furthermore, biocatalysts are known to possess chiral selectivity and specificity, a key focus of pharmaceutical drug design. In this review, we discuss how the explosion in genomics based sequence analysis, allied with parallel developments in synthetic and molecular biology, have the potential to fast-track the discovery and subsequent improvement of a new generation of marine biocatalysts.

SUBMITTER: Parages ML

PROVIDER: S-EPMC4810074 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts.

Parages María L ML Gutiérrez-Barranquero José A JA Reen F Jerry FJ Dobson Alan D W AD O'Gara Fergal F

Marine drugs 20160321 3

In recent years, the marine environment has been the subject of increasing attention from biotechnological and pharmaceutical industries as a valuable and promising source of novel bioactive compounds. Marine biodiscovery programmes have begun to reveal the extent of novel compounds encoded within the enormous bacterial richness and diversity of the marine ecosystem. A combination of unique physicochemical properties and spatial niche-specific substrates, in wide-ranging and extreme habitats, un ...[more]

PMID: 27007381

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Project description:The amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the 'search space' of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (Kd) and catalytic (kcat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving kcat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the 'best' amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole, simultaneously, this offers opportunities for protein improvement not readily available to natural evolution on rapid timescales. Intelligent landscape navigation, informed by sequence-activity relationships and coupled to the emerging methods of synthetic biology, offers scope for the development of novel biocatalysts that are both highly active and robust.

Dataset Information

Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts.

Publications

Integrated (Meta) Genomic and Synthetic Biology Approaches to Develop New Biocatalysts.

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