Indirect Pathway Metabolic Engineering Strategies for Enhanced Biosynthesis of Hyaluronic Acid in Engineered

Overview

Journal Front Bioeng Biotechnol

Date 2022 Jan 6

PMID 34988066

Citations 4

Authors

Yan Du

Fangyu Cheng

Miaomiao Wang

Chunmeng Xu

Huimin Yu

Affiliations

Soon will be listed here.

Abstract

Hyaluronic acid (HA) is composed of alternating d-glucuronic acid and -acetyl-d-glucosamine, with excellent biocompatibility and water retention capacity. To achieve heterologous biosynthesis of HA, , 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 gene knockout, releasing the inhibition of transporter IolT1/IolT2 and glucokinases; (2) intensification of cardiolipin synthesis through overexpression of genes // involved in cardiolipin synthesis; (3) duly expressed 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 .

Citing Articles

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Fine-tuning the cell morphology of via dual-valve regulation for enhanced hyaluronic acid production.

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