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.
Highlights
Metabolic engineering of microorganisms enables production of chemicals via construction and optimization of different metabolic pathways
This review describes the recent successful implementation and applications of co-cultivation methods for microbial biosynthesis using metabolic engineering approaches
This symbiotic consortium provides a balance in growth and product formation, where A. fermentans ferments cellulose to acetate and ethanol, which is further used by S. cerevisiae as a carbon and energy source, preventing accumulation of acetate and ethanol which inhibit the growth of A. fermentans (Bayer et al, 2009)
Summary
Metabolic engineering of microorganisms enables production of chemicals via construction and optimization of different metabolic pathways. To overcome the limitations posed by metabolic burden, significant developments have been made towards rationally designed microbial cocultures to distribute metabolic burden of complex and long biosynthetic pathways into different strains/species in order to improve bioproduction performance (Jones et al, 2017, 2016; Liu et al, 2018; Saini et al, 2015; Tsoi et al, 2018; Zhang and Wang, 2016) (Fig. 1) This approach has been inspired by microbial natural consortia, which carry out complex chemical reactions to provide favourable environment for survival of the community. Such approaches provide fine control of the target cells through
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