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Advances in regulating vitamin K2 production through metabolic engineering strategies

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Abstract

Vitamin K2 (menaquinone, VK2, MK) is an essential lipid-soluble vitamin that plays critical roles in inhibiting cell ferroptosis, improving blood clotting, and preventing osteoporosis. The increased global demand for VK2 has inspired interest in novel production strategies. In this review, various novel metabolic regulation strategies, including static and dynamic metabolic regulation, are summarized and discussed. Furthermore, the advantages and disadvantages of both strategies are analyzed in-depth to highlight the bottlenecks facing microbial VK2 production on an industrial scale. Finally, advanced metabolic engineering biotechnology for future microbial VK2 production will also be discussed. In summary, this review provides in-depth information and offers an outlook on metabolic engineering strategies for VK2 production.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Aguiar TQ, Silva R, Domingues L (2015) Ashbya gossypii beyond industrial riboflavin production: a historical perspective and emerging biotechnological applications. Biotechnol Adv 33:1774–1786

    Article  PubMed  CAS  Google Scholar 

  • Ahmed-Hocine B, Marius B, Georg S, Matthias M (2020) Rational engineering of transcriptional riboswitches leads to enhanced metabolite levels in Bacillus subtilis. Metab Eng 61

  • Altenbuchner J (2016) Editing of the Bacillus subtilis genome by the Crispr-cas9 system. Appl Environ Microbiol 82(17):5421–5427

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Anesiadis N, Cluett WR, Mahadevan R (2018) Dynamic metabolic engineering for increasing bioprocess productivity. Metab Eng 10:255–266

    Article  Google Scholar 

  • Arakawa C, Kuratsu M, Furihata K, Hiratsuka T, Itoh N, Seto H, Dairi T (2011) Diversity of the early step of the futalosine pathway. Antimicrob Agents Chemother 55(2):913

    Article  PubMed  CAS  Google Scholar 

  • Begley M, Gahan CG, Kollas AK, Hintz M, Hill C, Jomaa H, Eberl M (2004) The interplay between classical and alternative isoprenoid biosynthesis controls γδ T cell bioactivity of Listeria monocytogenes. FEBS Lett 561:99–104

    Article  PubMed  CAS  Google Scholar 

  • Berenjian A, Mahanama R, Talbot A, Regtop H, Kavanagh J, Dehghani F (2014) Designing of an intensification process for biosynthesis and recovery of menaquinone-7. Appl Biochem Biotechnol 172:1347–1357

    Article  PubMed  CAS  Google Scholar 

  • Bhalerao S, Clandinin TR (2012) Vitamin K2 takes charge. Science 336:1241–1242

    Article  PubMed  CAS  Google Scholar 

  • Binkley SB, Maccorquodale DW, Thayer A, Doisy EA (1939) The isolation of vitamin K1. J Biol Chem 130:219–234

    Article  CAS  Google Scholar 

  • Boucher Y, Doolittle WF (2000) The role of lateral gene transfer in the evolution of isoprenoid biosynthesis pathways. Mol Microbiol 37:703–716

    Article  PubMed  CAS  Google Scholar 

  • Boucher Y, Huber H, L’Haridon S, Stetter KO, Doolittle WF (2001) Bacterial origin for the isoprenoid biosynthesis enzyme HMG-CoA reductase of the archaeal orders Thermoplasmatales and Archaeoglobales. Mol Biol Evol 18:1378–1388

    Article  PubMed  CAS  Google Scholar 

  • Che J, Liu B, Liu G, Chen Q, Huang D (2018) Induced mutation breeding of Brevibacillus Brevis FJAT-0809-GLX for improving ethylparaben production and its application in the biocontrol of Lasiodiplodia theobromae. Postharvest Biol Technol 146:60–67

    Article  CAS  Google Scholar 

  • Chen L, Zeng AP (2017) Rational design and metabolic analysis of Escherichia coli for effective production of l-tryptophan at high concentration. Appl Microbiol Biotechnol 101:559–568

    Article  PubMed  CAS  Google Scholar 

  • Chen T, Xia H, Cui S, Lv X, Li X, Liu Y, Li J, Du G, Liu L (2020) Combinatorial methylerythritol phosphate pathway engineering and process optimization for increased menaquinone-7 synthesis in Bacillus subtilis. J Microbiol Biotechnol 30:762–769

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Choi SR, Larson MA, Hinrichs SH, Bartling AM, Frandsen J, Narayanasamy P (2016) Discovery of bicyclic inhibitors against menaquinone biosynthesis. Future Med Chem 8(1):11–16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Choi S, Lee HN, Park E, Lee SJ, Kim ES (2020) Recent advances in microbial production of cis, cis-muconic acid. Biomolecules 10:1238

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cotrim CA, Weidner A, Strehmel N, Bisol TB, Meyer D, Brandt W, Wessjohann PLA, Stubbs PMT (2017) A distinct aromatic prenyltransferase associated with the futalosine pathway. Chemistryselect 2(29):9319–9325

    Article  CAS  Google Scholar 

  • Cui S, Lv X, Wu Y, Li J, Du G, Ledesma-Amaro R, Liu L (2019) Engineering a bifunctional Phr60-Rap60-Spo0A quorum-sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis in Bacillus subtilis. ACS Synth Biol 8:1826–1837

    Article  PubMed  CAS  Google Scholar 

  • Cui S, Xia H, Chen T, Gu Y, Lv X, Liu YF, Li JH, Du GC, Liu L (2020) Cell membrane and electron transfer engineering for improved synthesis of menaquinone-7 in Bacillus subtilis. iScience 23(3):100918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dairi T (2012) Menaquinone biosyntheses in microorganisms. Meth Enzymol 515:107–122

    Article  CAS  Google Scholar 

  • Dam H (1967) Historical survey and introduction. Vitam Horm 24:295–306

    Article  Google Scholar 

  • Dam H (2010) The antihaemorrhagic vitamin of the chick. Nutr Rev 31(4):121–121

    Article  Google Scholar 

  • Ding XM, Zheng ZM, Zhao GH, Wang L, Wang H, Yang Q, Zhang MX, Li LY, Wang P (2022) Bottom–up synthetic biology approach for improving the efficiency of menaquinone–7 synthesis in Bacillus subtilis. Microb Cell Fact 21:101

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Eisenreich W, Rohdich F, Bacher A (2001) Deoxyxylulose phosphate pathway to terpenoids. Trends Plant Sci 6:78–84

    Article  PubMed  CAS  Google Scholar 

  • Frank A, Groll M (2017) The methylerythritol phosphate pathway to isoprenoids. Chem Rev 117:5675–5703

    Article  PubMed  CAS  Google Scholar 

  • Gao Q, Chen H, Wang W, Huang J, Tao Y, Lin B (2020) Menaquinone-7 production in engineered Escherichia coli. World J Microbiol Biotechnol 36(9):132

    Article  PubMed  CAS  Google Scholar 

  • Gao Q, Chen H, Wang G, Yang W, Zhong X, Liu J, Huo X, Liu W, Huang J, Tao Y, Lin B (2021) Highly efficient production of menaquinone-7 from glucose by metabolically engineered Escherichia coli. ACS Synth Biol 10(4):756–765

    Article  PubMed  CAS  Google Scholar 

  • García-Moyano A, Larsen Ø, Gaykawad S, Christakou E, Boccadoro C, Puntervoll P (2020) Fragment exchange plasmid tools for CRISPR/Cas9-mediated gene integration and protease production in Bacillus subtilis. Appl Environ Microbiol 87(1)

  • Goodman SR, Marrs BL, Narconis RJ, Olson RE (1976) Isolation and description of a menaquinone mutant from Bacillus licheniformis. J Bacteriol 125:282–289

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guo RT, Kuo CJ, Ko TP, Chou CC, Liang PH, Wang AH (2004) A molecular ruler for chain elongation catalyzed by octaprenyl pyrophosphate synthase and its structure-based engineering to produce unprecedented long chain trans-prenyl products. Biochemistry 43:7678–7686

    Article  PubMed  CAS  Google Scholar 

  • Halder M, Petsophonsakul P, Akbulut AC, Pavlic A, Bohan F, Anderson E, Maresz K, Kramann R, Schurgers L (2019) Vitamin K: double bonds beyond coagulation insights into differences between vitamin K1 and K2 in health and Disease. Int J Mol Sci 20:896

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Han X, Chen CC, Kuo CJ, Huang CH, Zheng Y, Ko TP (2015) Crystal structures of ligand-bound octaprenyl pyrophosphate synthase from Escherichia coli reveal the catalytic and chain-length determining mechanisms. Proteins 83:37–45

    Article  PubMed  CAS  Google Scholar 

  • Hao W, Suo F, Lin Q, Chen Qi, Zhou L, Liu Z (2020) Design and construction of portable CRISPR-cpf1-mediated genome editing in Bacillus subtilis 168 oriented toward multiple utilities. Front Bioeng Biotechnol 8:524676

    Article  PubMed  PubMed Central  Google Scholar 

  • Hiratsuka T, Furihata K, Ishikawa J, Yamashita H, Itoh N, Seto H, Dairi T (2008) An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321(5896):1670–1673

    Article  PubMed  CAS  Google Scholar 

  • Hiratsuka T, Itoh N, Seto H, Dairi T (2009) Enzymatic properties of futalosine hydrolase, an enzyme essential to a newly identified menaquinone biosynthetic pathway. Biosci Biotechnol Biochem 73(5):1137–1141

    Article  PubMed  CAS  Google Scholar 

  • Hong J, Park SH, Kim S, Kim SW, Hahn JS (2019) Efficient production of lycopene in Saccharomyces cerevisiae by enzyme engineering and increasing membrane flexibility and NADPH production. Appl Microbiol Biotechnol 103:211–223

    Article  PubMed  CAS  Google Scholar 

  • Ikeda M (2006) Towards bacterial strains overproducing l-tryptophan and other aromatics by metabolic engineering. Appl Microbiol Biot 69:615–626

    Article  CAS  Google Scholar 

  • Jiang M, Zhang H (2016) Engineering the shikimate pathway for biosynthesis of molecules with pharmaceutical activities in E. Coli. Curr Opin Biotechnol 42:1–6

    Article  PubMed  Google Scholar 

  • Johnston JM, Bulloch EM (2020) Advances in menaquinone biosynthesis: sublocalisation and allosteric regulation. Curr Opin Struct Biol 65:33–41

    Article  PubMed  CAS  Google Scholar 

  • Joshi S, Fedoseyenko D, Mahanta N, Manion H, Naseem S, Dairi T, Begley TP (2018) Novel enzymology in futalosine-dependent menaquinone biosynthesis. Curr Opin Chem Biol 47:134–141

    Article  PubMed  CAS  Google Scholar 

  • Kawamukai M (2018) Biosynthesis and applications of prenylquinones. Biosci Biotechnol Biochem 82:963–977

    Article  PubMed  CAS  Google Scholar 

  • Kim RQ, Offen WA, Davies GJ, Stubbs KA (2014) Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway. Acta Crystallogr 70(1):177–185

    CAS  Google Scholar 

  • Kim B, Binkley R, Kim HU, Lee SY (2018) Metabolic engineering of Escherichia coli for the enhanced production of l-tyrosine. Biotechnol Bioeng 115:2554–2564

    Article  PubMed  CAS  Google Scholar 

  • Kim H, Kim SY, Sim GY, Ahn JH (2020) Synthesis of 4-hydroxybenzoic acid derivatives in Escherichia coli. J Agric Food Chem 68:9743–9749

    Article  PubMed  CAS  Google Scholar 

  • Kong MK, 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

    Article  PubMed  CAS  Google Scholar 

  • Koyama T, Tajima M, Sano H, Doi T, Koike-Takeshita A, Obata S (1996) Identification of significant residues in the substrate binding site of Bacillus stearothermophilus farnesyl diphosphate synthase. Biochemistry 35:9533–9538

    Article  PubMed  CAS  Google Scholar 

  • Kuzuyama T (2017) Biosynthetic studies on terpenoids produced by Streptomyces. J Antibiot (Tokyo) 70:811–818

    Article  PubMed  CAS  Google Scholar 

  • Kuzuyama T, Seto H (2003) Diversity of the biosynthesis of the isoprene units. Nat Prod Rep 20:171–183

    Article  PubMed  CAS  Google Scholar 

  • Lal N, Berenjian A (2020) Cis and trans isomers of the vitamin menaquinone-7: which one is biologically significant? Appl Microbiol Biotechnol 104:2765–2776

    Article  PubMed  CAS  Google Scholar 

  • Lange BM, 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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laupitz R, Hecht S, Amslinger S, Zepeck F, Kaiser J, Richter G, Schramek N, Steinbacher S, Huber R, Arigoni D (2004) Biochemical characterization of Bacillus subtilis type II isopentenyl diphosphate isomerase, and phylogenetic distribution of isoprenoid biosynthesis pathways. Eur J Biochem 271:2658–2669

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Wendisch VF (2017) Biotechnological production of aromatic compounds of the extended shikimate pathway from renewable biomass. J Biotechnol 257:211–221

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Wang G (2016) Strategies of isoprenoids production in engineered bacteria. J Appl Microbiol 121:932–940

    Article  PubMed  CAS  Google Scholar 

  • Li Q, Fan F, Gao X, Yang C, Bi C, Tang J, Liu T, Zhang X (2017) Balanced activation of IspG and IspH to eliminate MEP intermediate accumulation and improve isoprenoids production in Escherichia coli. Metab Eng 44:13–21

    Article  PubMed  CAS  Google Scholar 

  • Lin Y, Shen X, Yuan Q, Yan Y (2013) Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin. Nat Commun 4:2603

    Article  PubMed  Google Scholar 

  • Liu Y, Wang L, Zheng ZM, Qiu HW, Wang P, Zhao GH, Gong GH, Song JY, Dai J (2015) Improvement of vitamin K2 production by Escherichia sp. with nitrogen ion beam implantation induction. Plasma Sci Technol 17(2):159–166

    Article  CAS  Google Scholar 

  • Liu Y, Ding XM, Xue ZL, Hu LX, Cheng Q, Chen MH, Su Y, Zhu B, Xu P (2017) Site-directed mutagenesis of UbiA to promote menaquinone biosynthesis in Elizabethkingia meningoseptica. Process Biochem 58:186–192

    Article  CAS  Google Scholar 

  • Liu Y, Yang ZM, Xue ZL, Qian SH, Wang Z, Hu LX, Wang J, Zhu H, Ding XM, Yu F (2018) Influence of site-directed mutagenesis of UbiA, overexpression of dxr, menA and ubiE, and supplementation with precursors on menaquinone production in Elizabethkingia meningoseptica. Process Biochem 68:64–72

    Article  CAS  Google Scholar 

  • Liu CL, Dong HG, Zhan J, Liu X, Yang Y (2019a) Multi-modular engineering for renewable production of isoprene via mevalonate pathway in Escherichia coli. J Appl Microbiol 126(4):1128–1139

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Niu H, Li Q, Gu P (2019b) Metabolic engineering for the production of l-phenylalanine in Escherichia coli. Biotech 9:85

    Google Scholar 

  • Liu SX, Li S, Shen GM, Sukumar N, Krezel AM, Li WK (2021) Structural basis of antagonizing the VK catalytic cycle for anticoagulation. Science 371:652401

    Article  Google Scholar 

  • Lv Y, Qian S, Du G, Chen J, Zhou J, Xu P (2019) Coupling feedback genetic circuits with growth phenotype for dynamic population control and intelligent bioproduction. Metab Eng 54:109–116

    Article  PubMed  CAS  Google Scholar 

  • Lyon GJ, Novick RP (2004) Peptide signaling in Staphylococcus aureus and other Gram-positive bacteria. Peptides 25:1389–1403

    Article  PubMed  CAS  Google Scholar 

  • Ma XC, Zhu SY, Luo MM, Hu XC, Peng C, Huang H, Ren LJ (2019a) Intracellular response of Bacillus natto in response to different oxygen supply and its influence on menaquinone-7 biosynthesis. Bioprocess Biosyst Eng 42:817–828

    Article  PubMed  CAS  Google Scholar 

  • Ma YW, McClure DD, Somerville MV, Proschogo NW, Dehghani F, KavanaghJM, Coleman NV (2019b) Metabolic engineering of the MEP pathway in Bacillus subtilis for increased biosynthesis of menaquinone-7. ACS Synth Biol 8(7):1620–1630

    Article  PubMed  CAS  Google Scholar 

  • Mahdinia E, Demirci A, Berenjian A (2017) Production and application of menaquinone-7 (vitamin K2): a new perspective. World J Microbiol Biotechnol 33:2

    Article  PubMed  Google Scholar 

  • Marles RJ, Roe AL, Oketch-Rabah HA (2017) US pharmacopeial convention safety evaluation of menaquinone-7, a form of vitamin K. Nutr Rev 75:553–578

    Article  PubMed  Google Scholar 

  • Marrero PF, Poulter CD, Edwards PA (1992) Effects of site-directed mutagenesis of the highly conserved aspartate residues in domain II of farnesyl diphosphate synthase activity. J Biol Chem 267:21873–21878

    Article  PubMed  CAS  Google Scholar 

  • Meganathan R (2001) Menaquinone and ubiquinone biosynthesis. Biochemistry 40(29):8641–8641

    Google Scholar 

  • Meganathan R, Kwon O (2011) Biosynthesis of menaquinone (vitamin K2) and ubiquinone (Coenzyme Q). EcoSal Plus 3(2):173–218

    Google Scholar 

  • Mishima E, Ito J, Wu ZJ, Nakamura T, Wahida A, Doll S, Tonnus W, Nepachalovich P, Eggenhofer E, Aldrovandi M, Henkelmann B, Yamada K, Wanninger J, Zilka O, Sato E, Feederle R, Hass D, Maida A, Mourão ASD, Linkermann A, Geissler EK, Nakagawa K, Abe T, Fedorova M, Proneth B, Pratt DA, Conrad M (2022) A non-canonical VK cycle is a potent ferroptosis suppressor. Nature 608:778–783

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Morishita T, Tamura N, Makino T, Kudo S (1999) Production of menaquinones by lactic acid bacteria. J Dairy Sci 82:1897–1903

    Article  PubMed  CAS  Google Scholar 

  • Noda S, Kondo A (2017) Recent advances in microbial production of aromatic chemicals and derivatives. Trends Biotechnol 35:785–796

    Article  PubMed  CAS  Google Scholar 

  • Partow S, Siewers V, Daviet L, Schalk M, Nielsen J (2012) Reconstruction and evaluation of the synthetic bacterial MEP pathway in Saccharomyces cerevisiae. PLoS ONE 7(12):e52498

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Paudel A, Hamamoto H, Panthee S, Sekimizu K (2016) Menaquinone as a potential target of antibacterial agents. Drug Discov Ther 10(3):123–128

    Article  PubMed  CAS  Google Scholar 

  • Puri A, Iqubal M, Zafar R, Panda BP (2015) Influence of physical, chemical and inducer treatments on menaquinone-7 biosynthesis by Bacillus subtilis MTCC 2756. Songklanakarin J Sci Technol 37:283–289

    CAS  Google Scholar 

  • Rekhter D, Ludke D, Ding Y, Feussner K, Zienkiewicz K, Lipka V, Wiermer M, Zhang Y, Feussner I (2019) Isochorismate-derived biosynthesis of the plant stress hormone salicylic acid. Science 365:498–502

    Article  PubMed  CAS  Google Scholar 

  • Rohmer M (2008) From molecular fossils of bacterial hopanoids to the formation of isoprene units: discovery and elucidation of the methylerythritol phosphate pathway. Lipids 43:1095–1107

    Article  PubMed  CAS  Google Scholar 

  • Sato T, Yamada Y, Ohtani Y, Mitsui N, Murasawa H, Araki S (2001) Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J Biosci Bioeng 91:16–20

    Article  PubMed  CAS  Google Scholar 

  • Shen YP, Fong LS, Yan ZB, Liu JZ (2019) Combining directed evolution of pathway enzymes and dynamic pathway regulation using a quorum-sensing circuit to improve the production of 4-hydroxyphenylacetic acid in Escherichia coli. Biotechnol Biofuels 12:94

    Article  PubMed  PubMed Central  Google Scholar 

  • Shimizu Y, Ogasawara Y, Matsumoto A, Dairi T (2018) Aplasmomycin and boromycin are specific inhibitors of the futalosine pathway. J Antibiot 71:968–970

    Article  CAS  Google Scholar 

  • Song J, Liu H, Wang L, Dai J, Zheng Z (2014) Enhanced production of vitamin K2 from Bacillus subtilis (natto) by mutation and optimization of the fermentation medium. Braz Arch Biol Technol 57:606–612

    CAS  Google Scholar 

  • Song Y, He S, Abdallah II, Jopkiewicz A, Setroikromo R, van Merkerk R (2021) Engineering of multiple modules to improve amorphadiene production in Bacillus subtilis using Crispr-Cas9. J Agric Food Chem 69(16):4785–4794

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tanaka R, Kunisada T, Kushida N, Yamada K, Ikeda S, Noike M, Ono Y, Itoh N, Takami H, Seto H (2011) Branched fatty acids inhibit the biosynthesis of menaquinone in Helicobacter pylori. J Antibiot 64(1):151–153

    Article  CAS  Google Scholar 

  • Tani Y, Asahi S, Yamada H (1986) Menaquinone (vitamin K2)-6 production by mutants of Flavobacterium meningosepticum. J Nutr Sci Vitaminol 32:137–145

    Article  PubMed  CAS  Google Scholar 

  • Tetali SD (2019) Terpenes and isoprenoids: a wealth of compounds for global use. Planta 249:1–8

    Article  PubMed  CAS  Google Scholar 

  • Tonhosolo R, D’Alexandri FL, Genta FA, Wunderlich G, Gozzo FC, Eberlin MN (2005) Identification, molecular cloning and functional characterization of an octaprenyl pyrophosphate synthase in intra-erythrocytic stages of Plasmodium Falciparum. Biochem J 392:117–126

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tsukamoto Y, Kasai M, Kakuda H (2001) Construction of a Bacillus subtilis (natto) with high productivity of vitamin K2 (menaquinone-7) by analog resistance. Biosci Biotechnol Biochem 65:2007–2015

    Article  PubMed  CAS  Google Scholar 

  • Vos M, Esposito G, Edirisinghe JN, Vilain S, Haddad DM, Slabbaert JR, Meensel SV, Schaap O, Strooper BD, Meganathan R, Morais VA, Verstreken P (2012) Vitamin K2 is a mitochondrial electron carrier that rescues Pink1 deficiency. Science 336:1306–1310

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Zada B, Wei G, Kim SW (2017) Metabolic engineering and synthetic biology approaches driving isoprenoid production in Escherichia coli. Bioresour Technol 241:430–438

    Article  PubMed  CAS  Google Scholar 

  • Wang Y, Liu L, Jin Z, Zhang D (2021) Microbial cell factories for green production of vitamins. Front Bioeng Biotechnol 9:661562

    Article  PubMed  PubMed Central  Google Scholar 

  • Westbrook AW, Moo-Young M, Chou CP (2016) Development of a Crispr-Cas9 tool kit for comprehensive engineering of Bacillus subtilis. Appl Environ Microbiol 82:4876–4895

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wu J, Li W, Zhao SG, Qian SH, Wang Z, Zhou MJ, Hu WS, Wang J, Hu LX, Liu Y, Xue ZL (2021) Site-directed mutagenesis of the quorum sensing transcriptional regulator SinR affects the biosynthesis of menaquinone in Bacillus subtilis. Microb Cell Fact 20(1):1–19

    Article  Google Scholar 

  • Xu P (2018) Production of chemicals using dynamic control of metabolic fluxes. Curr Opin Biotechnol 53:12–19

    Article  PubMed  CAS  Google Scholar 

  • Xu JZ, Zhang W (2017) Menaquinone-7 production from maize meal hydrolysate by Bacillus isolates with diphenylamine and analogue resistance. J Zhejiang Univ Sci B 18:462–473

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Xu L, Dmitry A, Gaynor EC, Tanner ME (2011) 5’-methylthioadenosine nucleosidase is implicated in playing a key role in a modified futalosine pathway for menaquinone biosynthesis in Campylobacter jejuni. J Biol Chem 286(22):19392–19398

    Article  Google Scholar 

  • Xu JZ, Yan WL, Zhang WG (2017) Enhancing menaquinone-7 production in recombinant Bacillus amyloliquefaciens by metabolic pathway engineering. RSC Adv 7(45):28527–28534

    Article  CAS  Google Scholar 

  • Yang SM, Cao YX, Sun LM, Li CF, Lin X, Cai ZG, Zhang GY, Song H (2019) Modular pathway engineering of Bacillus subtilis to promote de novo biosynthesis ofmenaquinone-7. ACS Synth Biol 8(1):70–81

    Article  PubMed  CAS  Google Scholar 

  • Yang Q, Zheng ZM, Zhao GH, Wang L, Wang H, Ding XM, Jiang CX, Li C, Ma GL, Wang P (2022) Engineering microbial consortia of Elizabethkingia meningoseptica and Escherichia coli strains for the biosynthesis of vitamin K2. Microb Cell Fact (2022) 21:37

  • Yu Y, Aairm R, Liu HR, Lv B, Chang PC, Song H, Wang Y, Li C (2020) Engineering Saccharomyces cerevisiae for high yield production of α-amyrin via synergistic remodeling of α-amyrin synthase and expanding the storage pool. Metab Eng 62:72–83

    Article  PubMed  CAS  Google Scholar 

  • Yuan P, Cui S, Liu Y, Li J, Lv X, Liu L, Du G (2020) Combinatorial engineering for improved menaquinone-4 biosynthesis in Bacillus subtilis. Enzyme Microb Technol 141:109652

    Article  PubMed  CAS  Google Scholar 

  • Yuan P, Sun G, Cui S, Wu Y, Lv X, Liu Y, Li J, Du G, Liu L (2021) Engineering a ComA quorum-sensing circuit to dynamically control the production of menaquinone-4 in Bacillus subtilis. Enzyme Microb Tech 147:109782

    Article  CAS  Google Scholar 

  • Zada B, Wang C, Park JB, Jeong SH, Park JE, Singh HB, Kim SW (2018) Metabolic engineering of Escherichia coli for production of mixed isoprenoid alcohols and their derivatives. Biotechnol Biofuels 11:210

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhi XY, Yao JC, Tang SK, Huang Y, Li HW, Li WJ (2014) The futalosine pathway played an important role in menaquinone biosynthesis during early prokaryote evolution. Genome Biol Evol 6:149–160

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou D, Maina SW, Zhang F, Yan Z, Xin Z (2020) Mining new plipastatins and increasing the total yield using Crispr/cas9 in genome modified Bacillus Subtilis 1A751. J Agric Food Chem 68(41):11358–11367

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The study was supported by the National Nature Science Foundation of China (No. 32372295), Outstanding Youth Research Project in Anhui Province Universities (No. 2023AH020013), Anhui university natural science research key project (2023AH050938), and Anhui Provincial Undergraduate Innovation and Entrepreneurship Program (No. 202310363254).

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Authors and Affiliations

  1. College of Biology and Food Engineering, Anhui Polytechnic University, 241000, Wuhu, China

    Yan Liu, Jian Wang, Jun-bao Huang, Xiang-fei Li, Yu Chen, Kun Liu, Ming Zhao, Xi-lin Huang, Xu-li Gao, Ya-ni Luo, Wei Tao, Jing Wu & Zheng-lian Xue

  2. Anhui Engineering Laboratory for Industrial Microbiology Molecular Breeding, 241000, Wuhu, China

    Yan Liu, Xiang-fei Li, Yu Chen, Kun Liu, Ming Zhao & Zheng-lian Xue

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  1. Yan Liu
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  11. Wei Tao
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Contributions

Yan Liu : conceptualization, review and editing, supervision, investigation, visualization. Jian Wang, Jun-bao Huang: methodology, writing—review and editing. Xiang-fei Li, Yu Chen, Kun Liu, Ming Zhao , Xi-lin Huang, Xu-li Gao, Ya-ni Luo, Wei Tao, Jing Wu: methodology, writing—original draft, review and editing. Zheng-lian Xue: supervision, writing—review and editing.

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Correspondence to Yan Liu or Ming Zhao.

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Liu, Y., Wang, J., Huang, Jb. et al. Advances in regulating vitamin K2 production through metabolic engineering strategies. World J Microbiol Biotechnol 40, 8 (2024). https://doi.org/10.1007/s11274-023-03828-5

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