Journal of Agricultural and Food Chemistry solated C10.Bioresour.Techno 012,116,241- no,Hi 35 U. ,539,23 o(4)2 rgetic 0L2009.258（6.4 f TCA cycle with ATP Theor. cid pr W. on f Fact 007(1).19. ,G.;Cam Xu.G.:Z ang,H:Zhu.E 00915（7.222 Le Set 2011.(5 g297 1)1 Bamba,T Bichs NX.2 7 Huerta-Beristain,G.:Gil 6mez,M Boli A.Impr ing po of the glut depen eAMB.E中r2017,7( 16)Mo,D.Yu,u Du.Che 33) .M Bog2011,108(12. Sci.Rep 2016,c 3 4 analys Gu,Yi of poly- s.1.Biol 2012,28 naintenance.APpl.Microbiol M:Ohta.Ri obe,A Y.i Y;Xu,Z;Li,S.;Feng X;Xu ic Fond 201 67.371 LChem.2019,294(, 36) n in Ba Cell Fact 2017,16 g0101.3s57-38 37) n.P:Itoh,Y 2tn -292 rege is WX-0 D: X;Xu,H.Enhan 2006,7826_-220 acid) 2016,63(⑤)，62 -632 n.N.Hof 40 He.Z:Chen,S.Enha ky,B.B;Sor E P riol2012,194(4 species in the B △1 D.:Wendisch.V.F.Lysin rod .291- n,Y.;Liu,L;Yang,S.;Ma,X:Chen,S (42)Sta N D.I B.A.Defn formis WX-02 App do stic stra (25)Zhang W.He Y Gao,W Feng Cao,M:Yang C Song 43 akul.S:Sone.C:Chisti.Y L Id 2015.(2).97305. A281 ction of poly 6.1424 133 hi,M.Prod 6273new isolated Bacillus subtilis C10. Bioresour. Technol. 2012, 116, 241− 246. (10) Cheng, C.; Asada, Y.; Aida, T. Production of γ-polyglutamic acid by Bacillus licheniformis A35 under denitrifying conditions. Agric. Biol. Chem. 1989, 53 (9), 2369−2375. (11) Feng, J.; Gu, Y.; Sun, Y.; Han, L.; Yang, C.; Zhang, W.; Cao, M.; Song, C.; Gao, W.; Wang, S. Metabolic engineering of Bacillus amyloliquefaciens for poly-gamma-glutamic acid (γ PGA) over￾production. Microb. Biotechnol. 2014, 7 (5), 446−455. (12) Feng, J.; Gu, Y.; Quan, Y.; Cao, M.; Gao, W.; Zhang, W.; Wang, S.; Yang, C.; Song, C. Improved poly-γ-glutamic acid production in Bacillus amyloliquefaciens by modular pathway engineering. Metab. Eng. 2015, 32, 106−115. (13) Huang, J.; Du, Y.; Xu, G.; Zhang, H.; Zhu, F.; Huang, L.; Xu, Z. High yield and cost-effective production of poly (γ glutamic acid) with Bacillus subtilis. Eng. Life. Sci. 2011, 11 (3), 291−297. (14) Tang, B.; Lei, P.; Xu, Z.; Jiang, Y.; Xu, Z.; Liang, J.; Feng, X.; Xu, H. Highly efficient rice straw utilization for poly-(γ-glutamic acid) production by Bacillus subtilis NX-2. Bioresour. Technol. 2015, 193, 370−376. (15) Zeng, W.; Chen, G.; Guo, Y.; Zhang, B.; Dong, M.; Wu, Y.; Wang, J.; Che, Z.; Liang, Z. Production of poly-γ-glutamic acid by a thermotolerant glutamate-independent strain and comparative anal￾ysis of the glutamate dependent difference. AMB. Express 2017, 7 (1), 213. (16) Mu, D.; Yu, X.; Xu, Z.; Du, Z.; Chen, G. Physiological and transcriptomic analyses reveal mechanistic insight into the adaption of marine Bacillus subtilis C01 to alumina nanoparticles. Sci. Rep 2016, 6, 29953. (17) Feng, J.; Gao, W.; Gu, Y.; Zhang, W.; Cao, M.; Song, C.; Zhang, P.; Sun, M.; Yang, C.; Wang, S. Functions of poly-gamma￾glutamic acid (gamma-PGA) degradation genes in gamma-PGA synthesis and cell morphology maintenance. Appl. Microbiol. Biotechnol. 2014, 98 (14), 6397−407. (18) Qiu, Y.; Zhu, Y.; Zhang, Y.; Sha, Y.; Xu, Z.; Li, S.; Feng, X.; Xu, H. Characterization of a regulator pgsR on endogenous plasmid p2Sip and its complementation for poly-(γ-glutamic acid) accumulation in Bacillus amyloliquefaciens. J. Agric. Food Chem. 2019, 67, 3711−3722. (19) Feng, J.; Gu, Y.; Quan, Y.; Gao, W.; Dang, Y.; Cao, M.; Lu, X.; Wang, Y.; Song, C.; Wang, S. Construction of energy-conserving sucrose utilization pathways for improving poly-γ-glutamic acid production in Bacillus amyloliquefaciens. Microb. Cell Fact 2017, 16 (1), 98. (20) Cai, D.; He, P.; Lu, X.; Zhu, C.; Zhu, J.; Zhan, Y.; Wang, Q.; Wen, Z.; Chen, S. A novel approach to improve poly-γ-glutamic acid production by NADPH regeneration in Bacillus licheniformis WX-02. Sci. Rep 2017, 7, 43404. (21) Tang, B.; Zhang, D.; Li, S.; Xu, Z.; Feng, X.; Xu, H. Enhanced poly (γ glutamic acid) production by H2O2-induced reactive oxygen species in the fermentation of Bacillus subtilis NX-2. Biotechnol. Appl. Biochem. 2016, 63 (5), 625−632. (22) Moses, S.; Sinner, T.; Zaprasis, A.; Stoveken, N.; Hoffmann, T.; Belitsky, B. R.; Sonenshein, A. L.; Bremer, E. Proline utilization by Bacillus subtilis: uptake and catabolism. J. Bacteriol. 2012, 194 (4), 745−758. (23) Georgi, T.; Rittmann, D.; Wendisch, V. F. Lysine and glutamate production by Corynebacterium glutamicum on glucose, fructose and sucrose: roles of malic enzyme and fructose-1, 6-bisphosphatase. Metab. Eng. 2005, 7 (4), 291−301. (24) Cai, D.; Hu, S.; Chen, Y.; Liu, L.; Yang, S.; Ma, X.; Chen, S. Enhanced production of poly-γ-glutamic acid by overexpression of the global anaerobic regulator Fnr in Bacillus licheniformis WX-02. Appl. Biochem. Biotechnol. 2018, 185 (4), 958−970. (25) Zhang, W.; He, Y.; Gao, W.; Feng, J.; Cao, M.; Yang, C.; Song, C.; Wang, S. Deletion of genes involved in glutamate metabolism to improve poly-gamma-glutamic acid production in B. amyloliquefaciens LL3. J. Ind. Microbiol. Biotechnol. 2015, 42 (2), 297−305. (26) Yao, J.; Xu, H.; Shi, N.; Cao, X.; Feng, X.; Li, S.; Ouyang, P. K. Analysis of carbon metabolism and improvement of γ-polyglutamic acid production from Bacillus subtilis NX-2. Appl. Biochem. Biotechnol. 2010, 160 (8), 2332−2341. (27) Zamboni, N.; Maaheimo, H.; Szyperski, T.; Hohmann, H. P.; Sauer, U. The phosphoenolpyruvate carboxykinase also catalyzes C3 carboxylation at the interface of glycolysis and the TCA cycle of Bacillus subtilis. Metab. Eng. 2004, 6 (4), 277−284. (28) Nazaret, C.; Heiske, M.; Thurley, K.; Mazat, J. P. Mitochondrial energetic metabolism: a simplified model of TCA cycle with ATP production. J. Theor. Biol. 2009, 258 (3), 455−464. (29) Tannler, S.; Decasper, S.; Sauer, U. Maintenance metabolism ̈ and carbon fluxes in Bacillus species. Microb. Cell Fact. 2008, 7 (1), 19. (30) Osera, C.; Amati, G.; Calvio, C.; Galizzi, A. SwrAA activates poly-γ-glutamate synthesis in addition to swarming in Bacillus subtilis. Microbiology 2009, 155 (7), 2282−2287. (31) Mitsunaga, H.; Meissner, L.; Palmen, T.; Bamba, T.; Büchs, J.; Fukusaki, E. Metabolome analysis reveals the effect of carbon catabolite control on the poly(gamma-glutamic acid) biosynthesis of Bacillus licheniformis ATCC 9945. J. Biosci. Bioeng 2016, 121 (4), 413−9. (32) Centeno-Leija, S.; Huerta-Beristain, G.; Giles-Gomez, M.; ́ Bolivar, F.; Gosset, G.; Martinez, A. Improving poly-3-hydroxybuty￾rate production in Escherichia coli by combining the increase in the NADPH pool and acetyl-CoA availability. Antonie van Leeuwenhoek 2014, 105 (4), 687−696. (33) Kim, Y. M.; Cho, H. S.; Jung, G. Y.; Park, J. M. Engineering the pentose phosphate pathway to improve hydrogen yield in recombinant Escherichia coli. Biotechnol. Bioeng. 2011, 108 (12), 2941−2946. (34) Rühl, M.; Le Coq, D.; Aymerich, S.; Sauer, U. 13C-flux analysis reveals NADPH-balancing transhydrogenation cycles in stationary phase of nitrogen-starving Bacillus subtilis. J. Biol. Chem. 2012, 287 (33), 27959−27970. (35) Hada, K.; Hirota, K.; Inanobe, A.; Kako, K.; Miyata, M.; Araoi, S.; Matsumoto, M.; Ohta, R.; Arisawa, M.; Daitoku, H.; Hanada, T.; Fukamizu, A. Tricarboxylic acid cycle activity suppresses acetylation of mitochondrial proteins during early embryonic development in Caenorhabditis elegans. J. Biol. Chem. 2019, 294 (9), 3091−3099. (36) Commichau, F. M.; Gunka, K.; Landmann, J. J.; Stülke, J. Glutamate metabolism in Bacillus subtilis: gene expression and enzyme activities evolved to avoid futile cycles and to allow rapid responses to perturbations of the system. J. Bacteriol. 2008, 190 (10), 3557−3564. (37) Kimura, K.; Tran, L. S. P.; Itoh, Y. Roles and regulation of the glutamate racemase isogenes, racE and yrpC, in Bacillus subtilis. Microbiology 2004, 150 (9), 2911−2920. (38) Lu, C. D. Pathways and regulation of bacterial arginine metabolism and perspectives for obtaining arginine overproducing strains. Appl. Microbiol. Biotechnol. 2006, 70 (3), 261−272. (39) Picossi, S.; Belitsky, B. R.; Sonenshein, A. L. Molecular Mechanism of the Regulation of Bacillus subtilis gltAB Expression by GltC. J. Mol. Biol. 2007, 365 (5), 1298−1313. (40) Li, B.; Cai, D.; Hu, S.; Zhu, A.; He, Z.; Chen, S. Enhanced synthesis of poly gamma glutamic acid by increasing the intracellular reactive oxygen species in the Bacillus licheniformis Δ1-pyrroline-5- carboxylate dehydrogenase gene ycgN-deficient strain. Appl. Microbiol. Biotechnol. 2018, 102 (23), 10127−10137. (41) Ohsawa, T.; Tsukahara, K.; Ogura, M. Bacillus subtilis response regulator DegU is a direct activator of pgsB transcription involved in γ- poly-glutamic acid synthesis. Biosci., Biotechnol., Biochem. 2009, 73 (9), 2096−2102. (42) Stanley, N. R.; Lazazzera, B. A. Defining the genetic differences between wild and domestic strains of Bacillus subtilis that affect poly γ DL glutamic acid production and biofilm formation. Mol. Microbiol. 2005, 57 (4), 1143−1158. (43) Cao, M.; Feng, J.; Sirisansaneeyakul, S.; Song, C.; Chisti, Y. Genetic and metabolic engineering for microbial production of poly- γ-glutamic acid. Biotechnol. Adv. 2018, 36, 1424−1433. (44) Kubota, H.; Matsunobu, T.; Uotani, K.; Takebe, H.; Satoh, A.; Tanaka, T.; Taniguchi, M. Production of poly (γ-glutamic acid) by Journal of Agricultural and Food Chemistry Article DOI: 10.1021/acs.jafc.9b01755 J. Agric. Food Chem. 2019, 67, 6263−6274 6273