Abstract
The bio-based production of added-value compounds (with applications as pharmaceuticals, biofuels, food ingredients, and building blocks) using bacterial platforms is a well-established industrial activity. The design and construction of microbial cell factories (MCFs) with robust and stable industrially relevant phenotypes, however, remains one of the biggest challenges of contemporary biotechnology. In this review, traditional and cutting-edge approaches for optimizing the performance of MCFs for industrial bioprocesses, rooted on the engineering principle of natural evolution (i.e., genetic variation and selection), are discussed. State-of-the-art techniques to manipulate and increase genetic variation in bacterial populations and to construct combinatorial libraries of strains, both globally (i.e., genome level) and locally (i.e., individual genes or pathways, and entire sections and gene clusters of the bacterial genome) are presented. Cutting-edge screening and selection technologies applied to isolate MCFs displaying enhanced phenotypes are likewise discussed. The review article is closed by presenting future trends in the design and construction of a new generation of MCFs that will contribute to the long-sought-after transformation from a petrochemical industry to a veritable sustainable bio-based industry.
Highlights
The use of microorganisms as platforms for the production of added-value compounds has a long tradition[1] and, over the years, has become a wellestablished industrial activity.[2]
The use of a inhibitor of uracil DNA glycosylase, in combination with a degradation tag, resulted in a more robust mutagenesis tool—allowing for the simultaneous, multiplex editing of six different genes. As this methodology does not rely on any host-dependent factor, it is extensible to other relevant bacterial species, e.g. C. glutamicum and Pseudomonas sp.[82]
The final objective of Systems Metabolic Engineering is the rational optimization of industrially-relevant phenotypes on microbial cell factory (MCF), the need for comprehensive molecular or functional knowledge and the availability of a dedicated Synthetic Biology toolbox are still major hurdles standing on the way towards purposefully engineering non-model bacteria
Summary
The development of efficient bacterial cell factories requires the optimization of phenotypic features at different levels of regulation. This review summarizes the major approaches that can be used for this purpose, including classical programs of mutagenesis and selection and cutting-edge technologies for targeted genome edition
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have