Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin
Authors
Sarnaik, Aditya
Abernathy, Mary H.
Han, Xiaorui
Ouyang, Yilan
Xia, Ke
Chen, Yin
Cress, Brady
Zhang, Fuming
Lali, Arvind
Pandit, Reena
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2019-01-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin, A. Sarnaika, M. H. Abernathy, X. Han, Y. Ouyang, K. Xia, Y. Chen, B. Cress, F. Zhang, A. Lali, R. Pandita, R. J. Linhardt, Y. J. Tang, M. A.G. Koffas, Algal Research 37 57–63, 2019.
Abstract
Heparosan is an unsulfated polysaccharide potentially important for its wide range of cosmetic and pharmaceutical applications, particularly as the precursor for the extensively used anticoagulant, heparin. Generally sourced from animals, commercially available heparin may encounter various immunological and contamination risks. Thus, safe and sustainable microbial platforms could serve as an alternative heparin source. Synechococcus, due to their fast photoautotrophic growth, strong sugar phosphate metabolisms and generally regarded as safe (GRAS) nature, may serve as photo-biorefineries for manufacturing heparosan. In this study, we have synthesized an integrative plasmid pUPm48 for cloning galU and PmHS2 genes in Synechococcus elongatus PCC 7942. The engineered recombinants (pgp7942) exhibited significant production of heparosan under different culture conditions, where the products were present in both supernatant and cell biomass. The maximum yield of 0.7 ± 0.2 μg/g-DCW (dry cell weight) and a titer of 2.8 ± 0.3 μg/L was achieved by pgp7942 under shake flask and continuous light conditions. Large scale plastic-bag cultures with natural diurnal light exhibited heparosan production of 0.5 μg/g-DCW with a titer of 0.44 μg/L. The analysis also found PCC 7942 encodes a promiscuous uridyltransferase for UDP-glucose synthesis and naturally produces multiple glycosaminoglycans including chondroitin sulfate (CS). This study demonstrates for the first-time cyanobacteria as a promising photoautotrophic refinery for producing a high-value polysaccharide commonly from animals.
Description
Algal Research 37 57–63
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Algal Research
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Algal Research
https://harc.rpi.edu/
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https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1016/j.algal.2018.11.010