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Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
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Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
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Journal Article
Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
2020
Overview
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.
Bioproduction of hyaluronan needs increases in yield and greater diversity of the molecular weights. Here, the author increases hyaluronan production and diversifies the molecular weights through engineering the hyaluronan biosynthesis pathway and disruption of
Corynebacterium glutamicum
encapsulation caused by secreted hyaluronan.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 38/70
/ 82/1
/ Bacterial Capsules - genetics
/ Bacterial Capsules - metabolism
/ Bacterial Proteins - genetics
/ Bacterial Proteins - metabolism
/ Batch Cell Culture Techniques - methods
/ Carbohydrate Metabolism - genetics
/ Corynebacterium glutamicum - enzymology
/ Corynebacterium glutamicum - genetics
/ Cytology
/ Humanities and Social Sciences
/ Hyaluronan Synthases - genetics
/ Hyaluronan Synthases - metabolism
/ Hyaluronic Acid - biosynthesis
/ Hyaluronoglucosaminidase - metabolism
/ Metabolic Engineering - methods
/ Metabolic Networks and Pathways - genetics
/ Polysaccharides, Bacterial - biosynthesis
/ Science
