Advances in the development and application of microbial consortia for metabolic engineering

Abstract

Recent advances in metabolic engineering enable the production of high-value chemicals via expressing complex biosynthetic pathways in a single microbial host. However, many engineered strains suffer from poor product yields due to redox imbalance and excess metabolic burden, and require compartmentalization of the pathway for optimal function. To address this problem, significant developments have been made towards co-cultivation of more than one engineered microbial strains to distribute metabolic burden between the co-cultivation partners and improve the product yield. In this emerging approach, metabolic pathway modules can be optimized separately in suitable hosts that will then be combined to enable optimal functionality of the complete pathway. This modular approach broadens the possibilities to fine tune sophisticated production platforms and thus achieve the biosynthesis of very complex compounds. Here, we review the different applications and the overall potential of natural and artificial co-cultivation systems in metabolic engineering in order to improve bioproduction/bioconversion. In addition to the several advantages over monocultures, major challenges and opportunities associated with co-cultivation are also discussed in this review.

Keywords: Co-cultivation; Microbial biosynthesis; Microbial consortia; Microbiome.

Fig. 1

Schematic representation of artificial consortium for bioproductions. (A) Co-cultivation comprising strains of the same species, (B) Co-cultivation comprising strains from different species and (C) Co-cultivation comprising mixed strains i.e. polyculture.

Fig. 2

Optimization of synthetic consortium for bioproductions. (A) Equal subpopulation of each constituent strain in consortium not always yield maximum product, (B) Tuning of strain subpopulation by changing the inoculation ratio to achieve high product yield and (C) swapping of the downstream strain in a plug-and-play manner allows production of various desired products from same intermediate.

Fig. 3

Schematic illustration of different types of co-cultivation systems. (A) Consolidated bioprocess for efficient degradation of lignocellulosic biomass and its utilization, (B) Nutritional divergence to avoid substrate competition between the co-cultivation partners, (C) Cross-feeding in microbial consortium, where one species survives on the side product of the other species while helping the producer to get rid of accumulated toxic side products, (D) Metabolic coupling between oxygenic photosynthesis and methane oxidation to convert greenhouse gasses into microbial biomass (E) Tunable cross-feeding module, where two auxotrophs control each other's growth via inducers. The inducer controls the production of essential metabolites for each partner, which must cross-feed in order to survive in the consortium, and (F) Intercellular complementation, where enzymes secreted out from each constituent strain of the consortium and formed a functional complex.