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dc.contributor.authorSarnaik, Aditya
dc.contributor.authorAbernathy, Mary H.
dc.contributor.authorHan, Xiaorui
dc.contributor.authorOuyang, Yilan
dc.contributor.authorXia, Ke
dc.contributor.authorChen, Yin
dc.contributor.authorCress, Brady
dc.contributor.authorZhang, Fuming
dc.contributor.authorLali, Arvind
dc.contributor.authorPandit, Reena
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorTang, Yinjie J.
dc.contributor.authorKoffas, Mattheos A.G.
dc.identifier.citationMetabolic 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.
dc.descriptionAlgal Research 37 57–63
dc.descriptionNote : 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.
dc.description.abstractHeparosan 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.
dc.description.sponsorshipNational Science Foundation
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofAlgal Research
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleMetabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin
dc.rights.holderIn Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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