Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin

Sarnaik, Aditya; Abernathy, Mary H.; Han, Xianlin; Ouyang, Yilan; Xia, Ke; Chen, Yin; Cress, Brady F.; Zhang, Fuming; Lali, Arvind; Pandit, Reena; Linhardt, Robert J.; Tang, Yinjie J.; Koffas, Mattheos

doi:10.1016/j.algal.2018.11.010

Cited by 43 publications

(18 citation statements)

References 34 publications

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“…PCC 7002 [16], makes it possible to genetically engineer this strain and regulate the expression of the target gene(s). Some examples of successful genetic engineering of cyanobacteria include genetic engineering for heparosan [17] and isobutanol production [18], in addition to direct photosynthetic production of biofuels and bioproducts [19]. However, Synechococcus sp.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of bicarbonate transporters in the marine cyanobacterium Synechococcus sp. PCC 7002 increases growth rate and glycogen accumulation

Gupta

Rai

Jain

et al. 2020

Biotechnol Biofuels

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Background: Synechococcus sp. PCC 7002 is an attractive organism as a feedstock and for photoautotrophic production of biofuels and biochemicals due to its fast growth and ability to grow in marine/brackish medium. Previous studies suggest that the growth of this organism is limited by the HCO 3 − transport across the cytoplasmic membrane. Tools for genetic engineering are well established for this cyanobacterium, which makes it possible to overexpress genes of interest. Results: In this work, we overexpressed two different native Na +-dependent carbon transporters viz., SbtA and BicA in Synechococcus sp. PCC 7002 cells under the influence of a strong light-inducible promoter and a strong RBS sequence. The overexpression of these transporters enhanced biomass by about 50%, increased intracellular glycogen about 50%, and increased extracellular carbohydrate up to threefold. Importantly, the biomass and glycogen productivity of the transformants with air bubbling was even higher than that of WT cells with 1% CO 2 bubbling. The overexpression of these transporters was associated with an increased carotenoid content without altering the chl a content. Conclusions: Our work shows the utility of increased carbon transport in improving the growth as well as product formation in a marine cyanobacterium and will serve to increase the utility of this organism as a potential cell factory.

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Section: Introductionmentioning

confidence: 99%

Overexpression of bicarbonate transporters in the marine cyanobacterium Synechococcus sp. PCC 7002 increases growth rate and glycogen accumulation

Gupta

Rai

Jain

et al. 2020

Biotechnol Biofuels

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“…Promising applications for this cyanobacterial strain include its use to produce biogenic polyphosphate nanoparticles to treat and prevent inflammatory gastrointestinal diseases ( Feng et al, 2018a , b , 2019 ), and hyaluronic acid, a natural polymer with a broad range of cosmetic and biomedical applications ( Zhang et al, 2019 ). Other attractive Synechococcus strains, such as Synechococcus elongatus PCC 7942 and the more recently characterized Synechococcus elongatus UTEX 2973 ( Yu et al, 2015 ), are already being used for the synthesis of bioactive molecules such as heparosan, a pharmaceutical precursor of heparin, and glycosaminoglycans ( Sarnaik et al, 2019 ), including heparan sulfate, chondroitin sulfate and hyaluronic acid, which play key roles in tissue maintenance, repair and regeneration ( Melrose, 2016 ).…”

Section: Transgenic Photosynthetic Organismsmentioning

confidence: 99%

Photosymbiosis for Biomedical Applications

Chávez

Moellhoff

Schenck

et al. 2020

Front. Bioeng. Biotechnol.

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Without the sustained provision of adequate levels of oxygen by the cardiovascular system, the tissues of higher animals are incapable of maintaining normal metabolic activity, and hence cannot survive. The consequence of this evolutionarily suboptimal design is that humans are dependent on cardiovascular perfusion, and therefore highly susceptible to alterations in its normal function. However, hope may be at hand. “Photosynthetic strategies,” based on the recognition that photosynthesis is the source of all oxygen, offer a revolutionary and promising solution to pathologies related to tissue hypoxia. These approaches, which have been under development over the past 20 years, seek to harness photosynthetic microorganisms as a local and controllable source of oxygen to circumvent the need for blood perfusion to sustain tissue survival. To date, their applications extend from the in vitro creation of artificial human tissues to the photosynthetic maintenance of oxygen-deprived organs both in vivo and ex vivo , while their potential use in other medical approaches has just begun to be explored. This review provides an overview of the state of the art of photosynthetic technologies and its innovative applications, as well as an expert assessment of the major challenges and how they can be addressed.

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“…1). Both of these UDP-sugars, as well as their precursors, are used for cyanobacterial cell wall biosynthesis and could theoretically be redirected to the biosynthesis of HA or similar polysaccharides [5].…”

Section: Overexpression Of Ha Synthase In Syn7002mentioning

confidence: 99%

“…However, apart from a very recent report on the production of heparosan [5], the use of cyanobacteria to produce pharmaceutically important polysaccharides remains relatively unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Photosynthetic conversion of CO2 to hyaluronic acid by engineered strains of the cyanobacterium Synechococcus sp. PCC 7002

et al. 2019

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Metabolic engineering of cyanobacteria for photoautotrophic production of heparosan, a pharmaceutical precursor of heparin

Cited by 43 publications

References 34 publications

Overexpression of bicarbonate transporters in the marine cyanobacterium Synechococcus sp. PCC 7002 increases growth rate and glycogen accumulation

Overexpression of bicarbonate transporters in the marine cyanobacterium Synechococcus sp. PCC 7002 increases growth rate and glycogen accumulation

Photosymbiosis for Biomedical Applications

Photosynthetic conversion of CO2 to hyaluronic acid by engineered strains of the cyanobacterium Synechococcus sp. PCC 7002

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