Chitin oligosaccharides (CTOs) and its related compounds chitosan oligosaccharides (CSOs), collectively known as chitooligosaccharides (COs), exhibit numerous biological activities in applications in the nutraceutical, cosmetics, agriculture, and pharmaceutical industries. COs are currently produced by acid hydrolysis of chitin or chitosan, or enzymatic techniques with uncontrollable polymerization. Microbial fermentation by recombinant Escherichia coli, as an alternative method for the production of COs, shows new potential because it can produce a well-defined COs mixture and is an environmentally friendly process. In addition, Bacillus subtilis, a nonpathogenic, endotoxin-free, GRAS status bacterium, presents a new opportunity as a platform to produce COs. Here, we review the applications of COs and differences between CTOs and CSOs, summarize the current preparation approaches of COs, and discuss the future research potentials and challenges in the production of well-defined COs in B. subtilis by metabolic engineering.

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