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l-Lactate treatment by photosynthetic cyanobacteria expressing heterogeneous l-lactate dehydrogenase

Kato, Yuichi Inabe, Kosuke Haraguchi, Yuji Shimizu, Tatsuya Kondo, Akihiko Hasunuma, Tomohisa 神戸大学

2023.05.04

概要

l-Lactate is a major waste compound in cultured animal cells. To develop a sustainable animal cell culture system, we aimed to study the consumption of l-lactate using a photosynthetic microorganism. As genes involved in l-lactate utilization were not found in most cyanobacteria and microalgae, we introduced the NAD-independent l-lactate dehydrogenase gene from Escherichia coli (lldD) into Synechococcus sp. PCC 7002. The lldD-expressing strain consumed l-lactate added to basal medium. This consumption was accelerated by expression of a lactate permease gene from E. coli (lldP) and an increase in culture temperature. Intracellular levels of acetyl-CoA, citrate, 2-oxoglutarate, succinate, and malate, and extracellular levels of 2-oxoglutarate, succinate, and malate, increased during l-lactate utilization, suggesting that the metabolic flux from l-lactate was distributed toward the tricarboxylic acid cycle. This study provides a perspective on l-lactate treatment by photosynthetic microorganisms, which would increase the feasibility of animal cell culture industries.

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Acknowledgements

We thank Ms. Aya Narita and Ms. Mami Matsuda for their technical assistance. This study was financially supported by the Cabinet Office, Government of Japan, Moonshot Research and Development Program.

Author contributions

Y.K.: Conceptualization, investigation, methodology, writing–original draft. K.I.: Investigation. Y.H.: Conceptualization, writing–review and editing. T.S.: Conceptualization, project administration. A.K.: Supervision. T.H.:

Project administration, writing–review and editing.

Competing interests The authors declare no competing interests.

Additional information

Supplementary Information The online version contains supplementary material available at https://​doi.​org/​

10.​1038/​s41598-​023-​34289-3.

Correspondence and requests for materials should be addressed to T.H.

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