Abstract
A large proportion of the recombinant proteins manufactured today rely on microbe-based expression systems owing to their relatively simple and cost-effective production schemes. However, several issues in microbial protein expression, including formation of insoluble aggregates, low protein yield, and cell death are still highly recursive and tricky to optimize. These obstacles are usually rooted in the metabolic capacity of the expression host, limitation of cellular translational machineries, or genetic instability. To this end, several microbial strains having precisely designed genomes have been suggested as a way around the recurrent problems in recombinant protein expression. Already, a growing number of prokaryotic chassis strains have been genome-streamlined to attain superior cellular fitness, recombinant protein yield, and stability of the exogenous expression pathways. In this review, we outline challenges associated with heterologous protein expression, some examples of microbial chassis engineered for the production of recombinant proteins, and emerging tools to optimize the expression of heterologous proteins. In particular, we discuss the synthetic biology approaches to design and build and test genome-reduced microbial chassis that carry desirable characteristics for heterologous protein expression.
Highlights
Heterologous protein expression by means of the genetically engineered prokaryotic host has made available a wide spectrum of recombinant proteins that are otherwise confined to limited natural origin, in a scalable and cost-effective manner
Catalogs of highly specialized microbial chassis are available for the functional expression of recombinant proteins with specific structural and biochemical demands (Table 1)
An increasing number of existing microbial chassis have been genome-streamlined to resolve some of the bottlenecks in heterologous protein expression and to further optimize their performance
Summary
Heterologous protein expression by means of the genetically engineered prokaryotic host has made available a wide spectrum of recombinant proteins that are otherwise confined to limited natural origin, in a scalable and cost-effective manner. Additional challenges include mimicking eukaryotic post-translational modifications (such as glycosylation) [11], production of harmful endotoxins (E. coli) [12], reduced cell viability resulting from unwanted by-products [13], and low protein yields [14] To tackle these obstacles, different recombinant DNA technologies, including manipulation of gene expression control [15,16,17], directing proper bond formation and protein folding [18,19], interfering host metabolic pathways [20,21], random or directed evolutions of bacterial strains or enzymes [22], and series of other methods have been systematically employed (summarized in [23]). Hosts of different microbial synthetic minimal genomes have been published to date (reviewed in [31]), with many harboring genetic and phenotypic traits to better house and support biosynthesis of heterologous proteins and commodity biomolecules
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