Micro-organisms have often been used to produce bioactive compounds as antibiotics, antifungals, and anti-tumors, etc. due to their easy and applicable culture, genetic manipulation, and extraction, etc. Mainly, microbial mono-cultures have been applied to produce value-added compounds and gotten numerous valuable results. However, mono-culture also has several complicated problems, such as metabolic burdens affecting the growth and development of the host, leading to a decrease in titer of the target compound. To circumvent those limitations, microbial co-culture has been technically developed and gained much interest compared to mono-culture. For example, co-culture simplifies the design of artificial biosynthetic pathways and restricts the recombinant host's metabolic burden, causing increased titer of desired compounds. This paper summarizes the recent advanced progress in applying microbial platform co-culture to produce natural products, such as flavonoid, terpenoid, alkaloid, etc. Furthermore, importantly different strategies for enhancing production, overcoming the metabolic burdens, building autonomous modulation of cell growth rate and culture composition in response to a quorum-sensing signal, etc., were also described in detail.
Keywords: Biosynthetic production; Co-culture; Metabolic engineering; Natural product.
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