Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum

Yang Wang, Litao Hu, Hao Huang, Hao Wang, Tianmeng Zhang, Jian Chen, Guocheng Du and Zhen Kang ()
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Yang Wang: Jiangnan University
Litao Hu: Jiangnan University
Hao Huang: Jiangnan University
Hao Wang: Jiangnan University
Tianmeng Zhang: Bloomage Biotechnology CO, LTD
Jian Chen: Jiangnan University
Guocheng Du: Jiangnan University
Zhen Kang: Jiangnan University

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Hyaluronan is widely used in cosmetics and pharmaceutics. Development of robust and safe cell factories and cultivation approaches to efficiently produce hyaluronan is of many interests. Here, we describe the metabolic engineering of Corynebacterium glutamicum and application of a fermentation strategy to manufacture hyaluronan with different molecular weights. C. glutamicum is engineered by combinatorial overexpression of type I hyaluronan synthase, enzymes of intermediate metabolic pathways and attenuation of extracellular polysaccharide biosynthesis. The engineered strain produces 34.2 g L−1 hyaluronan in fed-batch cultures. We find secreted hyaluronan encapsulates C. glutamicum, changes its cell morphology and inhibits metabolism. Disruption of the encapsulation with leech hyaluronidase restores metabolism and leads to hyper hyaluronan productions of 74.1 g L−1. Meanwhile, the molecular weight of hyaluronan is also highly tunable. These results demonstrate combinatorial optimization of cell factories and the extracellular environment is efficacious and likely applicable for the production of other biopolymers.

Date: 2020
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DOI: 10.1038/s41467-020-16962-7

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