Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator

Abstract Menaquinone-7 (MK-7) is a kind of vitamin K2 playing an important role in the treatment and prevention of cardiovascular disease, osteoporosis and arterial calcification. The purpose of this study is to establish an adaptive evolution strategy based on a chemical modulator to improve MK-7 b...

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Main Authors: Bei Zhang, Cheng Peng, Jianyao Lu, Xuechao Hu, Lujing Ren
Format: Article
Language:English
Published: SpringerOpen 2022-11-01
Series:Bioresources and Bioprocessing
Subjects:
Online Access:https://doi.org/10.1186/s40643-022-00609-0
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author Bei Zhang
Cheng Peng
Jianyao Lu
Xuechao Hu
Lujing Ren
author_facet Bei Zhang
Cheng Peng
Jianyao Lu
Xuechao Hu
Lujing Ren
author_sort Bei Zhang
collection DOAJ
description Abstract Menaquinone-7 (MK-7) is a kind of vitamin K2 playing an important role in the treatment and prevention of cardiovascular disease, osteoporosis and arterial calcification. The purpose of this study is to establish an adaptive evolution strategy based on a chemical modulator to improve MK-7 biosynthesis in Bacillus natto. The inhibitor of 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase), glyphosate, was chosen as the chemical modulator to perform the experiments. The final strain ALE-25–40, which was obtained after 40 cycles in 25 mmol/L glyphosate, showed a maximal MK-7 titer of 62 mg/L and MK-7 productivity of 0.42 mg/(L h), representing 2.5 and 3 times the original strain, respectively. Moreover, ALE-25–40 generated fewer spores and showed a higher NADH and redox potential. Furthermore, the mechanism related to the improved performance of ALE-25–40 was investigated by comparative transcriptomics analysis. Genes related to the sporation formation were down-regulated. In addition, several genes related to NADH formation were also up-regulated. This strategy proposed here may provide a new and alternative directive for the industrial production of vitamin K2. Graphical Abstract
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spelling doaj.art-71944e00e21943c2923c1a82d24857ce2022-12-22T04:20:22ZengSpringerOpenBioresources and Bioprocessing2197-43652022-11-019111210.1186/s40643-022-00609-0Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulatorBei Zhang0Cheng Peng1Jianyao Lu2Xuechao Hu3Lujing Ren4College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech UniversityCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech UniversityCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech UniversityCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech UniversityCollege of Biotechnology and Pharmaceutical Engineering, Nanjing Tech UniversityAbstract Menaquinone-7 (MK-7) is a kind of vitamin K2 playing an important role in the treatment and prevention of cardiovascular disease, osteoporosis and arterial calcification. The purpose of this study is to establish an adaptive evolution strategy based on a chemical modulator to improve MK-7 biosynthesis in Bacillus natto. The inhibitor of 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase), glyphosate, was chosen as the chemical modulator to perform the experiments. The final strain ALE-25–40, which was obtained after 40 cycles in 25 mmol/L glyphosate, showed a maximal MK-7 titer of 62 mg/L and MK-7 productivity of 0.42 mg/(L h), representing 2.5 and 3 times the original strain, respectively. Moreover, ALE-25–40 generated fewer spores and showed a higher NADH and redox potential. Furthermore, the mechanism related to the improved performance of ALE-25–40 was investigated by comparative transcriptomics analysis. Genes related to the sporation formation were down-regulated. In addition, several genes related to NADH formation were also up-regulated. This strategy proposed here may provide a new and alternative directive for the industrial production of vitamin K2. Graphical Abstracthttps://doi.org/10.1186/s40643-022-00609-0Menaquinone-7Bacillus nattoAdaptive evolutionGlyphosateEPSE synthase
spellingShingle Bei Zhang
Cheng Peng
Jianyao Lu
Xuechao Hu
Lujing Ren
Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
Bioresources and Bioprocessing
Menaquinone-7
Bacillus natto
Adaptive evolution
Glyphosate
EPSE synthase
title Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
title_full Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
title_fullStr Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
title_full_unstemmed Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
title_short Enhancing menaquinone-7 biosynthesis by adaptive evolution of Bacillus natto through chemical modulator
title_sort enhancing menaquinone 7 biosynthesis by adaptive evolution of bacillus natto through chemical modulator
topic Menaquinone-7
Bacillus natto
Adaptive evolution
Glyphosate
EPSE synthase
url https://doi.org/10.1186/s40643-022-00609-0
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