Abstract
Vitamin K2 plays an important role in electron transport, blood coagulation, and calcium homeostasis, and researchers have been trying to use microbes to produce it. Although our previous studies have shown that gradient radiation, breeding, and culture acclimation can improve vitamin K2 production in Elizabethkingia meningoseptica, the mechanism is still unclear. This study is the first which performs genome sequencing of E. meningoseptica sp. F2 as a basis for subsequent experiments and further comparative analyses with other strains. Comparative metabolic pathway analysis of E. meningoseptica sp. F2, E. coli, Bacillus subtilis, and other vitamin K2 product strains revealed that the mevalonate pathway of E. meningoseptica sp. F2 is different in bacteria at the system level. The expressions of menA, menD, menH, and menI in the menaquinone pathway and idi, hmgR, and ggpps in the mevalonate pathway were higher than those in the original strain. A total of 67 differentially expressed proteins involved in the oxidative phosphorylation metabolic pathway and citric acid cycle (TCA cycle) were identified. Our results reveal that combined gradient radiation breeding and culture acclimation can promote vitamin K2 accumulation probably by regulating the vitamin K2 pathway, oxidative phosphorylation metabolism pathway, and the citrate cycle (TCA cycle).
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Schurgers LJ, Knapen MHJ, Vermeer CJICS (2007) Vitamin K2 improves bone strength in postmenopausal women. Intl Cong Ser 1297:179–187. https://doi.org/10.1016/j.ics.2006.08.006
Vermeer C, Schurgers LJJHoCoNA (2000) A comprehensive review of vitamin K and vitamin K antagonists. Hematol Oncol Clin N 14:339–353. https://doi.org/10.1016/S0889-8588(05)70137-4
Wen L, Chen J, Duan L, Li SJMMR (2018) Vitamin K‑dependent proteins involved in bone and cardiovascular health (Review). Mol Med Rep 18. https://doi.org/10.3892/mmr.2018.8940
Bhalerao S, Clandinin TR (2012) Vitamin K2 takes charge. Science 336:1241–1242. https://doi.org/10.1126/science.1223812
Michio K, Eeshwaraiah B (2010) Vitamin K2 in electron transport system: Are enzymes involved in vitamin K2 biosynthesis promising drug targets? Molecules 15:1531–1553. https://doi.org/10.3390/molecules15031531
Vermeer C (2012) Vitamin K: The effect on health beyond coagulation-an overview. Food Nutr Res 56:5329–5334. https://doi.org/10.3402/fnr.v56i0.5329
Walther B, Karl JP, Booth SL, Boyaval P (2013) Menaquinones, bacteria, and the food supply: The relevance of dairy and fermented food products to vitamin K requirements. Adv Nutr 4:463–473. https://doi.org/10.3945/an.113.003855
Jean SS, Hsieh TC, Ning YZ, Hsueh PR (2017) Role of vancomycin in the treatment of bacteraemia and meningitis caused by Elizabethkingia meningoseptica. Int J Antimicrob AG 50. https://doi.org/10.1016/j.ijantimicag.2017.06.021
Kim KK, Kim MK, Lim JH, Park HY, Lee ST. (2005) Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov. Int J Syst Evol Microbiol. 55:1287–93. https://doi.org/10.1099/ijs.0.63541-0
Tani Y, Asahi S, Yamada H (1984) Vitamin K2 (Menaquinone) - Screening of producing microorganisms and production by flavobacterium–meningosepticum. J Ferment Technol 62:321–327
Taguchi H, Shibata T, Tani Y (1995) Selective release of menaquinone-4 from cells of a mutant of flavobacterium sp 238–7 with a detergent. Biosci Biotech Bioch 59:1137–1138. https://doi.org/10.1271/bbb.59.1137
Taguchi H, Shibata T, Duangmanee C, Tani Y (1989) Menaquinone-4 production by a sulfonamide: Resistant mutant of flavobacterium SP 238–7. Agric Biol Chem 53:3017–3023
Cunningham MJ (2019) OMICS Technologies
Chen S, Soehnlen M, Blom J, Terrapon N, Henrissat B, Walker E (2019) Comparative genomic analyses reveal diverse virulence factors and antimicrobial resistance mechanisms in clinical Elizabethkingia meningoseptica strains. PLoS ONE 14. https://doi.org/10.1371/journal.pone.0222648
Naidenov B, Lim A (2019) Pan-genomic and polymorphic driven prediction of antibiotic resistance in Elizabethkingia. Front Microbiol. https://doi.org/10.3389/fmicb.2019.01446
Schena L, Nigro F, Ippolito A, Gallitelli D (2004) Real-time quantitative PCR: A new technology to detect and study phytopathogenic and antagonistic fungi. Eur J Plant Pathol 110:893–908
Silva N, Ivamoto S, Camargo P, Rosa R, Pereira L, Domingues D (2020) Low-copy genes in terpenoid metabolism: The evolution and expression of MVK and DXR genes in angiosperms. Plants 9:525. https://doi.org/10.3390/plants9040525
Huang C, Fengguang Z, Lin Y, Zheng S, Liang S, Han S (2018) RNA-Seq analysis of global transcriptomic changes suggests a role for the MAPK pathway and carbon metabolism in cell wall maintenance in a Saccharomyces cerevisiae FKS1 mutant. Biochem Bioph Res Co 500
Chen C, Zheng Y, Zhong Y, Wu Y, Li Z, Xu L-A, Xu M (2018) Transcriptome analysis and identification of genes related to terpenoid biosynthesis in Cinnamomum camphora. BMC Genomics 19. https://https://doi.org/10.1186/s12864-018-4941-1
A XMT, A JLG, A LC, B CLHJJoP, Analysis B (2020) Application for proteomics analysis technology in studying animal-derived traditional Chinese medicine: A review. J Pharmaceut Biomed 191. https://doi.org/10.1016/j.jpba.2020.113609
Wu W, Wang G, Baek S, Shen R-F (2006) Comparative study of three proteomic quantitative methods, DIGE, cICAT, and iTRAQ, using 2D gel- or LC-MALDI TOF/TOF. J Proteome Res 5:651–658. https://doi.org/10.1021/pr050405o
Wu H, Wang H, Wang P, Zhao G, Zheng Z (2021) Gradient radiation breeding and culture domestication of menaquinone producing strains. Bioproc Biosyst Eng 44. https://doi.org/10.1007/s00449-021-02508-8
Fang X, Yang Q, Liu H, Wang P, Wang L, Zheng Z, Zhao G (2018) Effects of a combined processing technology involving ultrasound and surfactant on the metabolic synthesis of vitamin K2 by Flavobacterium sp. M1–14. Chem Eng Process 135. https://doi.org/10.1016/j.cep.2018.09.010
Bauer AW, Kirby WMM, Sherris JCA, Turck M (1966) Antibiotic susceptibility testing by a standardized single disk method. Tech bul Reg Med Tech 36:49–52. https://doi.org/10.1093/ajcp/45.4_ts.493
Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: Molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35:1547–1549
Lowe T, Eddy S (1997) tRNAscan-SE: A program for improved detection of transfer RNA Genes in genomic sequence. Nucleic Acids Res 25. https://doi.org/10.1093/nar/25.5.0955
Rocha D, Santos C, Pacheco L (2015) Bacterial reference genes for gene expression studies by RT-qPCR: survey and analysis. Anton Leeuw Int J G 108. https://doi.org/10.1007/s10482-015-0524-1
Livak K, Schmittgen T (2002) Analysis of relative gene expression data using real-time quantitative PCR. Methods (San Diego, Calif.) 25:402–408. https://doi.org/10.1006/meth.2001.1262
Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA (2009) Circos: An information aesthetic for comparative genomics. Genome Res 19:1639–1645. https://doi.org/10.1101/gr.092759.109
Coenye T (2003) (2003) Extracting phylogenetic information from whole-genome sequencing projects: the lactic acid bacteria as a test case. Microbiology 149:3507–3517. https://doi.org/10.1099/mic.0.26515-0
Woese CR, Kandler OML, Wheelis ML (1990) Towards a natural system of organisms: Proposal for the domains archaea, bacteria, and eucarya. Proc Natl Acad Sci USA 87:4576–4579. https://doi.org/10.1073/pnas.87.12.4576
Markus Lange B, Rujan T, Martin W, Croteau R (2000) Isoprenoid biosynthesis: The evolution of two ancient and distinct pathways across genomes. Proc Natl Acad Sci USA 97:13172–13177. https://doi.org/10.1073/pnas.240454797
Wei H, Zhao G, Liu H, Wang H, Ni W, Wang P, Zheng Z (2017) A simple and efficient method for the extraction and separation of menaquinone homologs from wet biomass of Flavobacterium. Bioproc Biosyst Eng. https://doi.org/10.1007/s00449-017-1851-6
Wei H, Wang L, Zhao G, Fang Z, Wu H, Wang P (2018) Zheng Z (2018) Extraction, purification and identification of menaquinones from Flavobacterium meningosepticum fermentation medium. Process Biochem 66:245–253. https://doi.org/10.1016/j.procbio.2018.01.007
Yang Q, Zheng Z, Zhao G, Wang L, Wang H, Ni W, Sun X, Zhang M, Tang H, Wang P (2002) Cloning and functional characterization of the geranylgeranyl diphosphate synthase(GGPPS)from Elizabethkingia meningoseptica sp.F2. Protein Expres Purif 189:105986. https://doi.org/10.1016/j.pep.2021.105986
Shaomei Y, Yingxiu C, Liming S, Congfa Li, Xue L (2018) Modular pathway engineering of Bacillus subtilis to promote de novo biosynthesis of menaquinone-7. Acs Synth Biol. https://doi.org/10.1021/acssynbio.8b00258
Xu JZ, Yan WL, Zhang WG (2017) Enhancing menaquinone-7 production in recombinant Bacillus amyloliquefaciens by metabolic pathway engineering. RSC Adv 7:28527–28534. https://doi.org/10.1039/C7RA03388E
Min KK, Lee PC (2011) Metabolic engineering of menaquinone 8 pathway of Escherichia coli as a microbial platform for vitamin K production. Biotechnol Bioeng 108:1997–2002. https://doi.org/10.1002/bit.23142
Pitera D, Paddon C, Newman J, Keasling J (2007) Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli. Metab Eng 9:193–207. https://doi.org/10.1016/j.ymben.2006.11.002
Chang M, Keasling J (2007) Production of isoprenoid pharmaceuticals by engineered microbes. Nat Chem Biol 2:674–681. https://doi.org/10.1038/nchembio836
Jones RW, Garland PB (1982) The function of Ubiquinone and Menaquinone in the respiratory chain of Escherichia coli. Fun Quin E Cons Syst 465–476. https://doi.org/10.1016/B978-0-12-701280-3:50039-6
Unden G, Bongaerts J (1997) Alternative respiratory pathways of Escherichia coli: energetics and transcriptional regulation in response to electron acceptors. BBA-Bioenergetics 1320:217–234. https://doi.org/10.1016/S0005-2728(97)00034-0
Yang Q, Zheng Z, Zhao G, Wang L, Wang H, Ding X, Jiang C, Li C, Ma G, Wang P (2022) Engineering microbial consortia of Elizabethkingia meningoseptica and Escherichia coli strains for the biosynthesis of vitamin K2. Microb Cell Fact 21:37. https://doi.org/10.1186/s12934-022-01768-7
Funding
This work was sponsored by financial support from National Natural Science Foundation of China (32070088), the China National Key Research and Development Programme (2019YFA0904300, 2019YFA0904304), Key Research and Development Plan of Anhui Province (1804b06020342), Major Projects of Science and Technology of Anhui Province (202103a06020003), and Natural Science Foundation of Anhui Province (1908085MB48 and 1908085MB43).
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ZZM and ZGH designed this study. YQ performed the research, analyzed the data, and wrote the paper; WP and WL participated in data analysis, figure preparation, and manuscript writing. WH and ZMX revised the manuscript.
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Yang, Q., Zheng, Z., Wang, P. et al. Insights into Regulating Mechanism of Mutagenesis Strains of Elizabethkingia meningoseptica sp. F2 by Omics Analysis. Curr Microbiol 80, 183 (2023). https://doi.org/10.1007/s00284-023-03270-8
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DOI: https://doi.org/10.1007/s00284-023-03270-8