Photosynthetic conversion of CO2 to hyaluronic acid by engineered strains of the cyanobacterium Synechococcus sp. PCC 7002
File(s)Zhang et al Algal Res 2019.pdf (605.35 KB)
Accepted version
Author(s)
Zhang, Lifang
Selão, Tiago Toscano
Nixon, Peter J
Norling, Birgitta
Type
Journal Article
Abstract
Hyaluronic acid (HA), consisting of alternating N-acetylglucosamine and glucuronic acid units, is a natural polymer with diverse cosmetic and medical applications. Currently, HA is produced by overexpressing HA synthases from gram-negative Pasteurella multocida (encoded by pmHAS) or gram-positive Streptococcus equisimilis (encoded by seHasA) in various heterotrophic microbial production platforms. Here we introduced these two different types of HA synthase into the fast-growing cyanobacterium Synechococcus sp. PCC 7002 (Syn7002) to explore the capacity for producing HA in a photosynthetic system. Our results show that both HA synthases enable Syn7002 to produce HA photoautotrophically, but that overexpression of the soluble HA synthase (PmHAS) is less deleterious to cell growth and results in higher production. Genetic disruption of the competing cellulose biosynthetic pathway increased the HA titer by over 5-fold (from 14 mg/L to 80 mg/L) and the relative proportion of HA with molecular mass greater than 2 MDa. Introduction of glmS and glmU, coding for enzymes involved in the biosynthesis of the precursor UDP-N-acetylglucosamine, in combination with partial glycogen depletion, allowed photosynthetic production of 112 mg/L of HA in 5 days, an 8-fold increase in comparison to the initial PmHAS expressing strain. Addition of tuaD and gtaB (coding for genes involved in UDP-glucuronic acid biosynthesis) also improved the HA yield, albeit to a lesser extent. Overall our results have shown that cyanobacteria hold promise for the sustainable production of pharmaceutically important polysaccharides from sunlight and CO2.
Date Issued
2019-12-01
Date Acceptance
2019-10-13
Citation
Algal Research, 2019, 44
ISSN
2211-9264
Publisher
Elsevier
Journal / Book Title
Algal Research
Volume
44
Copyright Statement
© 2019 Elsevier B.V. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Publication Status
Published
Article Number
ARTN 101702
Date Publish Online
2019-10-25