Enhanced Biosynthesis of Hyaluronic Acid Using Engineered Corynebacterium glutamicum Via Metabolic Pathway Regulation

2017 ◽  
Vol 12 (10) ◽  
pp. 1700191 ◽  
Author(s):  
Fangyu Cheng ◽  
Sijin Luozhong ◽  
Zhigang Guo ◽  
Huimin Yu ◽  
Gregory Stephanopoulos
Keyword(s):  
Hyaluronic Acid ◽  
Corynebacterium Glutamicum ◽  
Metabolic Pathway ◽  
Pathway Regulation

Engineering Corynebacterium glutamicum for high-titer biosynthesis of hyaluronic acid

2019 ◽  
Vol 55 ◽  
pp. 276-289 ◽  
Author(s):  
Fangyu Cheng ◽  
Huimin Yu ◽  
Gregory Stephanopoulos
Keyword(s):  
Hyaluronic Acid ◽  
Corynebacterium Glutamicum ◽  
High Titer

scholarly journals Indirect Pathway Metabolic Engineering Strategies for Enhanced Biosynthesis of Hyaluronic Acid in Engineered Corynebacterium glutamicum

2021 ◽  
Vol 9 ◽  
Author(s):  
Yan Du ◽  
Fangyu Cheng ◽  
Miaomiao Wang ◽  
Chunmeng Xu ◽  
Huimin Yu
Keyword(s):  
Hyaluronic Acid ◽  
Corynebacterium Glutamicum ◽  
Water Retention ◽  
Glucuronic Acid ◽  
Gene Knockout ◽  
Water Retention Capacity ◽  
Indirect Pathway ◽  
Retention Capacity ◽  
Heterologous Biosynthesis ◽  
Fed Batch Culture

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and N-acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, Corynebacterium glutamicum, a safe GRAS (generally recognized as safe) host, was utilized and metabolically engineered previously. In this work, to achieve further enhancement of HA yield, four strategies were proposed and performed separately first, i.e., (1) improvement of glucose uptake via iolR gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes pgsA1/pgsA2/cls involved in cardiolipin synthesis; (3) duly expressed Vitreoscilla hemoglobin in genome, enhancing HA titer coupled with more ATP and improved NAD+/NADH (>7.5) ratio; and (4) identification of the importance of glutamine for HA synthesis through transcriptome analyses and then enhancement of the HA titer via its supplement. After that, we combined different strategies together to further increase the HA titer. As a result, one of the optimal recombinant strains, Cg-dR-CLS, yielded 32 g/L of HA at 60 h in a fed-batch culture, which was increased by 30% compared with that of the starting strain. This high value of HA titer will enable the industrial production of HA via the engineered C. glutamicum.

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