Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions

Biotechnology Advances

Volumn 35, Issue 1, 2017, Pages 20-30

  Liu, Yanfeng ^a   Li, Jianghua ^a   Du, Guocheng ^a   Chen, Jian ^a   Liu, Long ^a  

^a JIANGNAN UNIVERSITY   (China)

Author keywords

Bacillus subtilis; Global metabolism optimization; Metabolic engineering; Systems biology

Indexed keywords

BACTERIOLOGY; METABOLISM; NETWORK LAYERS; PHYSIOLOGY;

BACILLUS SUBTILIS; COMPUTATIONAL MODEL; FUTURE PERSPECTIVES; MICROBIAL CELL FACTORIES; OMICS TECHNOLOGIES; PATHWAY ENGINEERINGS; REGULATORY MECHANISM; SYSTEMS BIOLOGY;

METABOLIC ENGINEERING;

BACTERIUM; BIOENGINEERING; CELLS AND CELL COMPONENTS; COMPUTER SIMULATION; DATA SET; METABOLISM; NUMERICAL MODEL; OPTIMIZATION;

BACILLUS SUBTILIS; BACTERIA (MICROORGANISMS);

BACILLUS SUBTILIS; BIOTECHNOLOGY; METABOLIC ENGINEERING; SYSTEMS BIOLOGY;

BACILLUS SUBTILIS; BIOTECHNOLOGY; METABOLIC ENGINEERING; SYSTEMS BIOLOGY;

EID: 85006851737     PISSN: 07349750     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.biotechadv.2016.11.003     Document Type: Review

References (147)

1. Ajikumar, P.K., Xiao, W.H., Tyo, K.E.J., Wang, Y., Simeon, F., Leonard, E., et al. Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science 330 (2010), 70–74.
2. Alper, H., Fischer, C., Nevoigt, E., Stephanopoulos, G., Tuning genetic control through promoter engineering. Proc. Natl. Acad. Sci. U. S. A. 102 (2005), 12678–12683.
3. Altenbuchner, J., Editing of the Bacillus subtilis genome by the CRISPR-Cas9 system. Appl. Environ. Microbiol. 82 (2016), 5421–5427.
4. 12) production in Bacillus megaterium. Microb. Biotechnol. 3 (2010), 24–37.
5. Biggs, B.W., De Paepe, B., Santos, C.N.S., De Mey, M., Ajikumar, P.K., Multivariate modular metabolic engineering or pathway and strain optimization. Curr. Opin. Biotechnol. 29 (2014), 156–162.
6. Bikard, D., Jiang, W., Samai, P., Hochschild, A., Zhang, F., Marraffini, L.A., Programmable repression and activation of bacterial gene expression using an engineered CRISPR-Cas system. Nucleic Acids Res. 41 (2013), 7429–7437.
7. Bodenmiller, B., Wanka, S., Kraft, C., Urban, J., Campbell, D., Pedrioli, P.G., et al. Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast. Sci. Signal., 3, 2010, s4.
8. Brinsmade, S.R., Alexander, E.L., Livny, J., Stettner, A.I., Segre, D., Rhee, K.Y., et al. Hierarchical expression of genes controlled by the Bacillus subtilis global regulatory protein CodY. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 8227–8232.
9. Brophy, J.A., Voigt, C.A., Principles of genetic circuit design. Nat. Methods 11 (2014), 508–520.
10. Brunk, E., George, K.W., Alonso-Gutierrez, J., Thompson, M., Baidoo, E., Wang, G., et al. Characterizing strain variation in engineered E. coli using a multi-omics-based workflow. Cell Syst. 2 (2016), 335–346.
11. Buescher, J.M., Liebermeister, W., Jules, M., Uhr, M., Muntel, J., Botella, E., et al. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism. Science 335 (2012), 1099–1103.
12. Bujara, M., Schümperli, M., Pellaux, R., Heinemann, M., Panke, S., Optimization of a blueprint for in vitro glycolysis by metabolic real-time analysis. Nat. Chem. Biol. 7 (2011), 271–277.
13. Caspeta, L., Chen, Y., Ghiaci, P., Feizi, A., Buskov, S., Hallström, B.M., et al. Altered sterol composition renders yeast thermotolerant. Science 346 (2014), 75–78.
14. Caspi, R., Altman, T., Billington, R., Dreher, K., Foerster, H., Fulcher, C.A., et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 42 (2014), D459–D471.
15. Castellana, M., Wilson, M.Z., Xu, Y., Joshi, P., Cristea, I.M., Rabinowitz, J.D., et al. Enzyme clustering accelerates processing of intermediates through metabolic channeling. Nat. Biotechnol. 32 (2014), 1011–1018.
16. Chen, L., Chen, Z., Zheng, P., Sun, J., Zeng, A.P., Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli. Appl. Microbiol. Biotechnol. 97 (2012), 2939–2949.
17. Chen, S., Xu, X.L., Grant, G.A., Allosteric activation and contrasting properties of L-serine dehydratase types 1 and 2. Biochemistry 51 (2012), 5320–5328.
18. Chen, T., Liu, W., Fu, J., Zhang, B., Tang, Y., Engineering Bacillus subtilis for acetoin production from glucose and xylose mixtures. J. Biotechnol. 168 (2013), 499–505.
19. Chen, Y., Nielsen, J., Advances in metabolic pathway and strain engineering paving the way for sustainable production of chemical building blocks. Curr. Opin. Biotechnol. 24 (2013), 965–972.
20. Chen, Z., Bommareddy, R.R., Frank, D., Rappert, S., Zeng, A.-P., Deregulation of feedback inhibition of phosphoenolpyruvate carboxylase for improved lysine production in Corynebacterium glutamicum. Appl. Environ. Microbiol. 80 (2014), 1388–1393.
21. Chen, Z., Rappert, S., Zeng, A.-P., Rational design of allosteric regulation of homoserine dehydrogenase by a non-natural inhibitor L-lysine. ACS Synth. Biol. 4 (2015), 126–131.
22. Chou, H.H., Keasling, J.D., Programming adaptive control to evolve increased metabolite production. Nat. Commun., 4, 2013, 2595.
23. Chubukov, V., Gerosa, L., Kochanowski, K., Sauer, U., Coordination of microbial metabolism. Nat. Rev. Microbiol. 12 (2014), 327–340.
24. Chubukov, V., Uhr, M., Le Chat, L., Kleijn, R.J., Jules, M., Link, H., et al. Transcriptional regulation is insufficient to explain substrate-induced flux changes in Bacillus subtilis. Mol. Syst. Biol., 9, 2013, 709.
25. Commichau, F.M., Alzinger, A., Sande, R., Bretzel, W., Reuß, D.R., Dormeyer, M., et al. Engineering Bacillus subtilis for the conversion of the antimetabolite 4-hydroxy-L-threonine to pyridoxine. Metab. Eng. 29 (2015), 196–207.
26. Commichau, F.M., Rothe, F.M., Herzberg, C., Wagner, E., Hellwig, D., Lehnik-Habrink, M., et al. Novel activities of glycolytic enzymes in Bacillus subtilis interactions with essential proteins involved in mRNA processing. Mol. Cell. Proteomics 8 (2009), 1350–1360.
27. Cress, B.F., Trantas, E.A., Ververidis, F., Linhardt, R.J., Koffas, M.A.G., Sensitive cells: enabling tools for static and dynamic control of microbial metabolic pathways. Curr. Opin. Biotechnol. 36 (2015), 205–214.
28. Cross, P.J., Allison, T.M., Dobson, R.C., Jameson, G.B., Parker, E.J., Engineering allosteric control to an unregulated enzyme by transfer of a regulatory domain. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 2111–2116.
29. Curran, K.A., Karim, A.S., Gupta, A., Alper, H.S., Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications. Metab. Eng. 19 (2013), 88–97.
30. Curran, K.A., Morse, N.J., Markham, K.A., Wagman, A.M., Gupta, A., Alper, H.S., Short, synthetic terminators for improved heterologous gene expression in yeast. ACS Synth. Biol. 4 (2015), 824–832.
31. Deng, M.D., Severson, D.K., Grund, A.D., Wassink, S.L., Burlingame, R.P., Berry, A., et al. Metabolic engineering of Escherichia coli for industrial production of glucosamine and N-acetylglucosamine. Metab. Eng. 7 (2005), 201–214.
32. Deng, M.D., Grund, A.D., Wassink, S.L., Peng, S.S., Nielsen, K.L., Huckins, B.D., et al. Directed evolution and characterization of Escherichia coli glucosamine synthase. Biochimie 88 (2006), 419–429.
33. Derouiche, A., Shi, L., Bidnenko, V., Ventroux, M., Pigonneau, N., Franz-Wachtel, M., et al. Bacillus subtilis SalA is a phosphorylation-dependent transcription regulator that represses ScoC and activates the production of the exoprotease AprE. Mol. Microbiol. 97 (2015), 1195–1208.
34. Dong, H., Zhang, D., Current development in genetic engineering strategies of Bacillus species. Microb. Cell Factories, 13, 2014, 63.
35. Dormeyer, M., Egelkamp, R., Thiele, M.J., Hammer, E., Gunka, K., Stannek, L., et al. A novel engineering tool in the Bacillus subtilis toolbox: inducer-free activation of gene expression by selection-driven promoter decryptification. Microbiology 161 (2014), 354–361.
36. Dragosits, M., Mattanovich, D., Adaptive laboratory evolution – principles and applications for biotechnology. Microb. Cell Factories, 12, 2013, 64.
37. Dueber, J.E., Wu, G.C., Malmirchegini, G.R., Moon, T.S., Petzold, C.J., Ullal, A.V., et al. Synthetic protein scaffolds provide modular control over metabolic flux. Nat. Biotechnol. 27 (2009), 753–759.
38. Elsholz, A.K.W., Turgay, K., Michalik, S., Hessling, B., Gronau, K., Oertel, D., et al. Global impact of protein arginine phosphorylation on the physiology of Bacillus subtilis. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 7451–7456.
39. Feng, J., Gu, Y., Quan, Y., Cao, M., Gao, W., Zhang, W., et al. Improved poly-γ-glutamic acid production in Bacillus amyloliquefaciens by modular pathway engineering. Metab. Eng. 32 (2015), 106–115.
40. Feng, Y., De Franceschi, G., Kahraman, A., Soste, M., Melnik, A., Boersema, P.J., et al. Global analysis of protein structural changes in complex proteomes. Nat. Biotechnol. 32 (2014), 1036–1044.
41. Fu, J., Wang, Z., Chen, T., Liu, W., Shi, T., Wang, G., et al. NADH plays the vital role for chiral pure D-(-)-2, 3-butanediol production in Bacillus subtilis under limited oxygen conditions. Biotechnol. Bioeng. 111 (2014), 2126–2131.
42. Gaballa, A., Antelmann, H., Aguilar, C., Khakh, S.K., Song, K.-B., Smaldone, G.T., et al. The Bacillus subtilis iron-sparing response is mediated by a fur-regulated small RNA and three small, basic proteins. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 11927–11932.
43. Gao, T., Ho, K.-P., L-lactic acid production by Bacillus subtilis MUR1 in continuous culture. J. Biotechnol. 168 (2013), 646–651.
44. Garavaglia, S., Galizzi, A., Rizzi, M., Allosteric regulation of Bacillus subtilis NAD kinase by quinolinic acid. J. Bacteriol. 185 (2003), 4844–4850.
45. Geng, F., Chen, Z., Zheng, P., Sun, J., Zeng, A.P., Exploring the allosteric mechanism of dihydrodipicolinate synthase by reverse engineering of the allosteric inhibitor binding sites and its application for lysine production. Appl. Microbiol. Biotechnol. 97 (2012), 1963–1971.
46. Georg, J., Hess, W.R., Cis-antisense RNA, another level of gene regulation in bacteria. Microbiol. Mol. Biol. Rev. 75 (2011), 286–300.
47. Gerosa, L., Sauer, U., Regulation and control of metabolic fluxes in microbes. Curr. Opin. Biotechnol. 22 (2011), 566–575.
48. Gerwig, J., Kiley, T.B., Gunka, K., Stanley-Wall, N., Stülke, J., The protein tyrosine kinases EpsB and PtkA differentially affect biofilm formation in Bacillus subtilis. Microbiology 160 (2014), 682–691.
49. Guan, C., Cui, W., Cheng, J., Zhou, L., Guo, J., Hu, X., et al. Construction and development of an auto-regulatory gene expression system in Bacillus subtilis. Microb. Cell Factories, 14, 2015, 150.
50. Harvie, D.R., Andreini, C., Cavallaro, G., Meng, W., Connolly, B.A., Yoshida, K., et al. Predicting metals sensed by ArsR-SmtB repressors: allosteric interference by a non-effector metal. Mol. Microbiol. 59 (2006), 1341–1356.
51. Heidrich, N., Moll, I., Brantl, S., In vitro analysis of the interaction between the small RNA SR1 and its primary target ahrC mRNA. Nucleic Acids Res. 35 (2007), 4331–4346.
52. Higgins, D., Dworkin, J., Recent progress in Bacillus subtilis sporulation. FEMS Microbiol. Rev. 36 (2012), 131–148.
53. Holtz, W.J., Keasling, J.D., Engineering static and dynamic control of synthetic pathways. Cell 140 (2010), 19–23.
54. Humphrey, S.J., Azimifar, S.B., Mann, M., High-throughput phosphoproteomics reveals in vivo insulin signaling dynamics. Nat. Biotechnol. 33 (2015), 990–995.
55. Hutchison, C.A. III, Chuang, R.-Y., Noskov, V.N., Assad-Garcia, N., Deerinck, T.J., Ellisman, M.H., et al. Design and synthesis of a minimal bacterial genome. Science, 351(6280), 2016 (aad6253).
56. Irnov, I., Sharma, C.M., Vogel, J., Winkler, W.C., Identification of regulatory RNAs in Bacillus subtilis. Nucleic Acids Res. 38 (2010), 6637–6651.
57. Jakutyte-Giraitiene, L., Gasiunas, G., Design of a CRISPR-Cas system to increase resistance of Bacillus subtilis to bacteriophage SPP1. J. Ind. Microbiol. Biotechnol. 43 (2016), 1183–1188.
58. Jin, P., Zhang, L., Yuan, P., Kang, Z., Du, G., Chen, J., Efficient biosynthesis of polysaccharides chondroitin and heparosan by metabolically engineered Bacillus subtilis. Carbohydr. Polym. 140 (2016), 424–432.
59. Jin, P., Kang, Z., Yuan, P., Du, G., Chen, J., Production of specific-molecular-weight hyaluronan by metabolically engineered Bacillus subtilis 168. Metab. Eng. 35 (2016), 21–30.
60. Juhas, M., Reuß, D., Zhu, B., Commichau, F.M., Bacillus subtilis and Escherichia coli essential genes and minimal cell factories after one decade of genome engineering. Microbiology 160 (2014), 2341–2351.
61. Juminaga, D., Baidoo, E.E., Redding-Johanson, A.M., Batth, T.S., Burd, H., Mukhopadhyay, A., et al. Modular engineering of L-tyrosine production in Escherichia coli. Appl. Environ. Microbiol. 78 (2012), 89–98.
62. Kabisch, J., Pratzka, I., Meyer, H., Albrecht, D., Lalk, M., Ehrenreich, A., et al. Metabolic engineering of Bacillus subtilis for growth on overflow metabolites. Microb. Cell Factories, 12, 2013, 72.
63. Kiley, T.B., Stanley-wall, N.R., Post-translational control of Bacillus subtilis biofilm formation mediated by tyrosine phosphorylation. Mol. Microbiol. 78 (2010), 947–963.
64. Kobir, A., Poncet, S., Bidnenko, V., Delumeau, O., Jers, C., Zouhir, S., et al. Phosphorylation of Bacillus subtilis gene regulator AbrB modulates its DNA-binding properties. Mol. Microbiol. 92 (2014), 1129–1141.
65. Kohlstedt, M., Sappa, P.K., Meyer, H., Maaß, S., Zaprasis, A., Hoffmann, T., et al. Adaptation of Bacillus subtilis carbon core metabolism to simultaneous nutrient limitation and osmotic challenge: a multi-omics perspective. Environ. Microbiol. 16 (2014), 1898–1917.
66. Kushwaha, M., Salis, H.M., A portable expression resource for engineering cross-species genetic circuits and pathways. Nat. Commun., 6, 2015, 7832.
67. Li, X., Gianoulis, T.A., Yip, K.Y., Gerstein, M., Snyder, M., Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses. Cell 143 (2010), 639–650.
68. Licona-Cassani, C., Lara, A.R., Cabrera-Valladares, N., Escalante, A., Hernández-Chávez, G., Martinez, A., et al. Inactivation of pyruvate kinase or the phosphoenolpyruvate: sugar phosphotransferase system increases shikimic and dehydroshikimic acid yields from glucose in Bacillus subtilis. J. Mol. Microbiol. Biotechnol. 24 (2013), 37–45.
69. Liebeton, K., Lengefeld, J., Eck, J., The nucleotide composition of the spacer sequence influences the expression yield of heterologously expressed genes in Bacillus subtilis. J. Biotechnol. 191 (2014), 214–220.
70. Link, H., Kochanowski, K., Sauer, U., Systematic identification of allosteric protein-metabolite interactions that control enzyme activity in vivo. Nat. Biotechnol. 31 (2013), 357–361.
71. Liu, L., Liu, Y., Shin, H.-d., Chen, R.R., Wang, N.S., Li, J., et al. Developing Bacillus spp. as a cell factory for production of microbial enzymes and industrially important biochemicals in the context of systems and synthetic biology. Appl. Microbiol. Biotechnol. 97 (2013), 6113–6127.
72. Liu, R., Bassalo, M.C., Zeitoun, R.I., Gill, R.T., Genome scale engineering techniques for metabolic engineering. Metab. Eng. 32 (2015), 143–154.
73. Liu, Y., Link, H., Liu, L., Du, G., Chen, J., Sauer, U., A dynamic pathway analysis approach reveals a limiting futile cycle in N-acetylglucosamine overproducing Bacillus subtilis. Nat. Commun., 7, 2016, 11933.
74. Liu, Y., Liu, L., Shin, H.-d., Chen, R.R., Li, J., Du, G., et al. Pathway engineering of Bacillus subtilis for microbial production of N-acetylglucosamine. Metab. Eng. 19 (2013), 107–115.
75. Liu, Y., Zhu, Y., Li, J., H-d, S., Chen, R.R., Du, G., et al. Modular pathway engineering of Bacillus subtilis for improved N-acetylglucosamine production. Metab. Eng. 23 (2014), 42–52.
76. Liu, Y., Zhu, Y., Ma, W., H-d, S., Li, J., Liu, L., et al. Spatial modulation of key pathway enzymes by DNA-guided scaffold system and respiration chain engineering for improved N-acetylglucosamine production by Bacillus subtilis. Metab. Eng. 24 (2014), 61–69.
77. Lomenick, B., Olsen, R.W., Huang, J., Identification of direct protein targets of small molecules. ACS Chem. Biol. 6 (2011), 34–46.
78. Maaß, S., Wachlin, G., Bernhardt, J., Eymann, C., Fromion, V., Riedel, K., et al. Highly precise quantification of protein molecules per cell during stress and starvation responses in Bacillus subtilis. Mol. Cell. Proteomics 13 (2014), 2260–2276.
79. Macek, B., Mijakovic, I., Olsen, J.V., Gnad, F., Kumar, C., Jensen, P.R., et al. The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus subtilis. Mol. Cell. Proteomics 6 (2007), 697–707.
80. Mali, P., Esvelt, K.M., Church, G.M., Cas9 as a versatile tool for engineering biology. Nat. Methods 10 (2013), 957–963.
81. Marchadier, E., Carballido-López, R., Brinster, S., Fabret, C., Mervelet, P., Bessières, P., et al. An expanded protein-protein interaction network in Bacillus subtilis reveals a group of hubs: exploration by an integrative approach. Proteomics 11 (2011), 2981–2991.
82. Mars, R.A.T., Mendonca, K., Denham, E.L., van Dijl, J.M., The reduction in small ribosomal subunit abundance in ethanol-stressed cells of Bacillus subtilis is mediated by a SigB-dependent antisense RNA. BBA-Mol. Cell. Res. 1853 (2015), 2553–2559.
83. Mars, R.A.T., Nicolas, P., Ciccolini, M., Reilman, E., Reder, A., Schaffer, M., et al. Small regulatory RNA-induced growth rate heterogeneity of Bacillus subtilis. PLoS Genet., 11, 2015, e1005046.
84. McFedries, A., Schwaid, A., Saghatelian, A., Methods for the elucidation of protein-small molecule interactions. Chem. Biol. 20 (2013), 667–673.
85. McNerney, M.P., Watstein, D.M., Styczynski, M.P., Precision metabolic engineering: the design of responsive, selective, and controllable metabolic systems. Metab. Eng. 31 (2015), 123–131.
86. Meile, J.C., Wu, L.J., Ehrlich, S.D., Errington, J., Noirot, P., Systematic localisation of proteins fused to the green fluorescent protein in Bacillus subtilis: identification of new proteins at the DNA replication factory. Proteomics 6 (2006), 2135–2146.
87. Meyer, A., Pellaux, R., Potot, S., Becker, K., Hohmann, H.-P., Panke, S., et al. Optimization of a whole-cell biocatalyst by employing genetically encoded product sensors inside nanolitre reactors. Nat. Chem. 7 (2015), 673–678.
88. Meyer, F.M., Gerwig, J., Hammer, E., Herzberg, C., Commichau, F.M., Völker, U., et al. Physical interactions between tricarboxylic acid cycle enzymes in Bacillus subtilis: evidence for a metabolon. Metab. Eng. 13 (2011), 18–27.
89. Meyer, H., Weidmann, H., Mäder, U., Hecker, M., Völker, U., Lalk, M., A time resolved metabolomics study: the influence of different carbon sources during growth and starvation of Bacillus subtilis. Mol. BioSyst. 10 (2014), 1812–1823.
90. Michna, R.H., Commichau, F.M., Toedter, D., Zschiedrich, C.P., Stuelke, J., SubtiWiki-a database for the model organism Bacillus subtilis that links pathway, interaction and expression information. Nucleic Acids Res. 42 (2014), D692–D698.
91. Mijakovic, I., Deutscher, J., Protein-tyrosine phosphorylation in Bacillus subtilis: a 10-year retrospective. Front. Microbiol. 6 (2015), 108–113.
92. Mijakovic, I., Poncet, S., Boël, G., Mazé, A., Gillet, S., Jamet, E., et al. Transmembrane modulator-dependent bacterial tyrosine kinase activates UDP-glucose dehydrogenases. EMBO J. 22 (2003), 4709–4718.
93. Moon, T.S., Dueber, J.E., Shiue, E., Prather, K.L.J., Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli. Metab. Eng. 12 (2010), 298–305.
94. Morimoto, T., Kadoya, R., Endo, K., Tohata, M., Sawada, K., Liu, S., et al. Enhanced recombinant protein productivity by genome reduction in Bacillus subtilis. DNA Res. 15 (2008), 73–81.
95. Mu, L., Wen, J., Engineered Bacillus subtilis 168 produces L-malate by heterologous biosynthesis pathway construction and lactate dehydrogenase deletion. World J. Microbiol. Biotechnol. 29 (2013), 33–41.
96. E). Mol. Cell. Proteomics 13 (2014), 1008–1019.
97. Na, D., Yoo, S.M., Chung, H., Park, H., Park, J.H., Lee, S.Y., Metabolic engineering of Escherichia coli using synthetic small regulatory RNAs. Nat. Biotechnol. 31 (2013), 170–174.
98. Nicolas, P., Mäder, U., Dervyn, E., Rochat, T., Leduc, A., Pigeonneau, N., et al. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science 335 (2012), 1103–1106.
99. Nowroozi, F.F., Baidoo, E.E., Ermakov, S., Redding-Johanson, A.M., Batth, T.S., Petzold, C.J., et al. Metabolic pathway optimization using ribosome binding site variants and combinatorial gene assembly. Appl. Microbiol. Biotechnol. 98 (2013), 1567–1581.
100. Oliveira, A.P., Ludwig, C., Picotti, P., Kogadeeva, M., Aebersold, R., Sauer, U., Regulation of yeast central metabolism by enzyme phosphorylation. Mol. Syst. Biol., 8, 2012, 623.
101. Oliveira, A.P., Ludwig, C., Zampieri, M., Weisser, H., Aebersold, R., Sauer, U., Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis. Sci. Signal., 8, 2015, rs4.
102. Oliveira, A.P., Sauer, U., The importance of post-translational modifications in regulating Saccharomyces cerevisiae metabolism. FEMS Yeast Res. 12 (2012), 104–117.
103. Orsak, T., Smith, T.L., Eckert, D., Lindsley, J.E., Borges, C.R., Rutter, J., Revealing the allosterome: systematic identification of metabolite-protein interactions. Biochemistry 51 (2012), 225–232.
104. Peters, J.M., Colavin, A., Shi, H., Czarny, T.L., Larson, M.H., Wong, S., et al. A comprehensive, CRISPR-based functional analysis of essential genes in bacteria. Cell 165 (2016), 1493–1506.
105. Perkins, J., Wyss, M., Dauner, M., Sauer, U., Hohmann, H.P., Metabolic engineering of B. subtilis. Smolke, C.D., Nielsen, J., (eds.) Metabolic Pathway Engineering Handbook, 2009, CRC press.
106. Phan, T.T.P., Nguyen, H.D., Schumann, W., Construction of a 5′-controllable stabilizing element (CoSE) for over-production of heterologous proteins at high levels in Bacillus subtilis. J. Biotechnol. 168 (2013), 32–39.
107. Qi, H., Li, S., Zhao, S., Huang, D., Xia, M., Wen, J., Model-driven redox pathway manipulation for improved isobutanol production in Bacillus subtilis complemented with experimental validation and metabolic profiling analysis. PLoS One, 9, 2014, e93815.
108. Radeck, J., Kraft, K., Bartels, J., Cikovic, T., Dürr, F., Emenegger, J., et al. The Bacillus BioBrick box: generation and evaluation of essential genetic building blocks for standardized work with Bacillus subtilis. J. Biol. Eng., 7, 2013, 29.
109. Raman, S., Taylor, N., Genuth, N., Fields, S., Church, G.M., Engineering allostery. Trends Genet. 30 (2014), 521–528.
110. Ravikumar, V., Shi, L., Krug, K., Derouiche, A., Jers, C., Cousin, C., et al. Quantitative phosphoproteome analysis of Bacillus subtilis reveals novel substrates of the kinase PrkC and phosphatase PrpC. Mol. Cell. Proteomics 13 (2014), 1965–1978.
111. Rudner, D.Z., Losick, R., Protein subcellular localization in bacteria. Cold Spring Harb. Perspect. Biol., 2, 2010, a000307.
112. Salzberg, L.I., Botella, E., Hokamp, K., Antelmann, H., Maaß, S., Becher, D., et al. A genome-wide analysis of PhoP ∼ P binding to chromosomal DNA reveals several novel features of the PhoPR-mediated phosphate limitation response in Bacillus subtilis. J. Bacteriol. 197 (2015), 1492–1506.
113. Sander, J.D., Joung, J.K., CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol. 32 (2014), 347–355.
114. Schilling, O., Frick, O., Herzberg, C., Ehrenreich, A., Heinzle, E., Wittmann, C., et al. Transcriptional and metabolic responses of Bacillus subtilis to the availability of organic acids: transcription regulation is important but not sufficient to account for metabolic adaptation. Appl. Environ. Microbiol. 73 (2007), 499–507.
115. Schmidt, A., Trentini, D.B., Spiess, S., Fuhrmann, J., Ammerer, G., Mechtler, K., et al. Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response. Mol. Cell. Proteomics 13 (2014), 537–550.
116. Schulz, J.C., Zampieri, M., Wanka, S., von Mering, C., Sauer, U., Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways. Sci. Signal., 7, 2014, rs6.
117. Scoffone, V., Dondi, D., Biino, G., Borghese, G., Pasini, D., Galizzi, A., et al. Knockout of pgdS and ggt genes improves γ-PGA yield in B. subtilis. Biotechnol. Bioeng. 110 (2013), 2006–2012.
118. Shapiro, L., McAdams, H.H., Losick, R., Why and how bacteria localize proteins. Science 326 (2009), 1225–1228.
119. Shen, B., Zhang, W., Zhang, J., Zhou, J., Wang, J., Chen, L., et al. Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects. Nat. Methods 11 (2014), 399–402.
120. Shetty, R.P., Endy, D., Knight, T.F. Jr., Engineering BioBrick vectors from BioBrick parts. J. Biol. Eng., 2, 2008, 5.
121. Shi, T., Wang, Y., Wang, Z., Wang, G., Liu, D., Fu, J., et al. Deregulation of purine pathway in Bacillus subtilis and its use in riboflavin biosynthesis. Microb. Cell Factories, 13, 2014, 101.
122. Shulman, A., Zalyapin, E., Vyazmensky, M., Yifrach, O., Ze, B., Chipman, D.M., Allosteric regulation of Bacillus subtilis threonine deaminase, a biosynthetic threonine deaminase with a single regulatory domain. Biochemistry 47 (2008), 11783–11792.
123. Sierro, N., Makita, Y., de Hoon, M., Nakai, K., DBTBS: a database of transcriptional regulation in Bacillus subtilis containing upstream intergenic conservation information. Nucleic Acids Res. 36 (2008), D93–D96.
124. Smaldone, G.T., Revelles, O., Gaballa, A., Sauer, U., Antelmann, H., Helmann, J.D., A global investigation of the Bacillus subtilis Iron-sparing response identifies major changes in metabolism. J. Bacteriol. 194 (2012), 2594–2605.
125. Sonenshein, A.L., Control of key metabolic intersections in Bacillus subtilis. Nat. Rev. Microbiol. 5 (2007), 917–927.
126. Storz, G., Vogel, J., Wassarman, K.M., Regulation by small RNAs in bacteria: expanding frontiers. Mol. Cell 43 (2011), 880–891.
127. Tanaka, K., Tajima, S., Takenaka, S., Yoshida, K.-I., An improved Bacillus subtilis cell factory for producing scyllo-inositol, a promising therapeutic agent for Alzheimer's disease. Microb. Cell Factories, 12, 2013, 124.
128. Toya, Y., Hirasawa, T., Ishikawa, S., Chumsakul, O., Morimoto, T., Liu, S., et al. Enhanced dipicolinic acid production during the stationary phase in Bacillus subtilis by blocking acetoin synthesis. Biosci. Biotechnol. Biochem. 79 (2015), 2073–2080.
129. Trentini, D.B., Fuhrmann, J., Mechtler, K., Clausen, T., Chasing phosphoarginine proteins: development of a selective enrichment method using a phosphatase trap. Mol. Cell. Proteomics 13 (2014), 1953–1964.
130. van Dijl, J.M., Hecker, M., Bacillus subtilis: from soil bacterium to super-secreting cell factory. Microb. Cell Factories, 12, 2013, 3.
131. Wang, B.L., Ghaderi, A., Zhou, H., Agresti, J., Weitz, D.A., Fink, G.R., et al. Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption. Nat. Biotechnol. 32 (2014), 473–478.
132. Wang, Y., Chen, Z., Zhao, R., Jin, T., Zhang, X., Chen, X., Deleting multiple lytic genes enhances biomass yield and production of recombinant proteins by Bacillus subtilis. Microb. Cell Factories, 13, 2014, 129.
133. Welsch, N., Homuth, G., Schweder, T., Stepwise optimization of a low-temperature Bacillus subtilis expression system for “difficult to express” proteins. Appl. Microbiol. Biotechnol. 99 (2015), 6363–6376.
134. Westbrook, A.W., Moo-Young, M., Chou, C.P., Development of a CRISPR-Cas9 toolkit for comprehensive engineering of Bacillus subtilis. Appl. Environ. Microbiol., 2016, 10.1128/AEM.01159-16.
135. Westers, H., Dorenbos, R., van Dijl, J.M., Kabel, J., Flanagan, T., Devine, K.M., et al. Genome engineering reveals large dispensable regions in Bacillus subtilis. Mol. Biol. Evol. 20 (2003), 2076–2090.
136. Wiedenheft, B., Sternberg, S.H., Doudna, J.A., RNA-guided genetic silencing systems in bacteria and archaea. Nature 482 (2012), 331–338.
137. Xu, P., Gu, Q., Wang, W., Wong, L., Bower, A.G., Collins, C.H., et al. Modular optimization of multi-gene pathways for fatty acids production in E. coli. Nat. Commun., 4, 2013, 1409.
138. Xue, D., Abdallah, I.I., de Haan, I.E., Sibbald, M.J., Quax, W.J., Enhanced C30 carotenoid production in Bacillus subtilis by systematic overexpression of MEP pathway genes. Appl. Microbiol. Biotechnol. 99 (2015), 5907–5915.
139. Yang, J., Seo, S.W., Jang, S., Shin, S.-I., Lim, C.H., Roh, T.-Y., et al. Synthetic RNA devices to expedite the evolution of metabolite-producing microbes. Nat. Commun., 4, 2013, 1413.
140. Yang, S., Kang, Z., Cao, W., Du, G., Chen, J., Construction of a novel, stable, food-grade expression system by engineering the endogenous toxin-antitoxin system in Bacillus subtilis. J. Biotechnol. 19 (2016), 40–47.
141. Yang, T., Rao, Z., Hu, G., Zhang, X., Liu, M., Dai, Y., et al. Metabolic engineering of Bacillus subtilis for redistributing the carbon flux to 2,3-butanediol by manipulating NADH levels. Biotechnol. Biofuels, 8, 2015, 129.
142. Zelcbuch, L., Antonovsky, N., Bar-Even, A., Levin-Karp, A., Barenholz, U., Dayagi, M., et al. Spanning high-dimensional expression space using ribosome-binding site combinatorics. Nucleic Acids Res., 41, 2013, e98.
143. Zhang, B., Li, N., Wang, Z., Tang, Y.-J., Chen, T., Zhao, X., Inverse metabolic engineering of Bacillus subtilis for xylose utilization based on adaptive evolution and whole-genome sequencing. Appl. Microbiol. Biotechnol. 99 (2014), 885–896.
144. Zhang, K., Duan, X., Wu, J., Multigene disruption in undomesticated Bacillus subtilis ATCC 6051a using the CRISPR/Cas9 system. Sci. Rep., 6, 2016, 27943.
145. Zhang, X., Zhang, R., Bao, T., Rao, Z., Yang, T., Xu, M., et al. The rebalanced pathway significantly enhances acetoin production by disruption of acetoin reductase gene and moderate-expression of a new water-forming NADH oxidase in Bacillus subtilis. Metab. Eng. 23 (2014), 34–41.
146. Zhao, H., Sun, Y., Peters, J.M., Gross, C.A., Garner, E.C., Helmann, J.D., Depletion of undecaprenyl pyrophosphate phosphatases disrupts cell envelope biogenesis in Bacillus subtilis. J. Bacteriol. 198:21 (2016), 2925–2935.
147. Zhu, H., Yang, S.-M., Yuan, Z.-M., Ban, R., Metabolic and genetic factors affecting the productivity of pyrimidine nucleoside in Bacillus subtilis. Microb. Cell Factories, 14, 2015, 54.