Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum
Biotechnology paper published in Nature Communications (2020)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Leech hyaluronidase disrupts the polysaccharide capsule encapsulating engineered Corynebacterium glutamicum, restoring metabolism and elevating hyaluronan production from 34.2 g/L to 74.1 g/L.
Warum dies für die Hirudotherapie relevant ist
This metabolic engineering study describes modification of Corynebacterium glutamicum for hyaluronan production, achieving 34.2 g/L in fed-batch cultures and 74.1 g/L after disruption of HA-induced cell encapsulation with leech hyaluronidase, with tunable molecular weights. The leech enzyme is employed to degrade the secreted HA capsule that encapsulates bacterial cells and inhibits metabolism, thereby restoring growth and dramatically boosting yields. The connection to ASH's domain is limited to the use of a leech-derived hyaluronidase as a bioprocessing reagent in industrial fermentation. No leeches, hirudotherapy, clinical applications, or leech secretome characterization beyond this specific enzyme are involved, and the study's relevance is confined to biotechnological exploitation of a leech enzyme.
Zitation
Eliminating the capsule-like layer to promote glucose uptake for hyaluronan production by engineered Corynebacterium glutamicum.
Wang Y et al. · Nature Communications, 2020
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