科微学术

生物工程学报

2025年4月5日 18:39 星期六
首页 > 过刊浏览>2023年第39卷第6期 >2430-2448. DOI:10.13345/j.cjb.221010
PDF HTML阅读 XML下载 导出引用 引用提醒
甲醇生物转化合成化学品的研究进展
作者:
基金项目:

国家重点研发计划(2018YFA0901500)；国家自然科学基金(22078151， 22178169， 22008113)；中国科协青年人才托举工程(YESS20200174)


Advances in biotransformation of methanol into chemicals
Author:
  • 摘要
    • | |
  • 访问统计
    • |
  • 参考文献 [63]
    • |
  • 相似文献 [20]
    • |
  • 引证文献
    • | |
  • 文章评论
    摘要:

    甲醇来源丰富、价格低廉，已成为生物制造行业极具吸引力的底物之一。构建微生物细胞工厂实现甲醇到增值化学品的生物转化，具有过程绿色、条件温和、产品体系多样等优势，不仅能拓展基于甲醇的产品链，还能缓解当前生物制造“与民争粮、与粮争地”的问题，是实现绿色生物制造的重要手段。因此，阐明不同天然甲基营养菌中涉及甲醇氧化、甲醛同化和异化途径对于后续基因工程改造工作至关重要，也更有利于构建新型非天然甲基营养菌。本文讨论了甲基营养菌中甲醇代谢途径的研究现状，并结合近年来天然和人工合成甲基营养菌在甲醇生物转化中的应用进展及面临的挑战。

    Abstract:

    Methanol has become an attractive substrate for the biomanufacturing industry due to its abundant supply and low cost. The biotransformation of methanol to value-added chemicals using microbial cell factories has the advantages of green process, mild conditions and diversified products. These advantages may expand the product chain based on methanol and alleviate the current problem of biomanufacturing, which is competing with people for food. Elucidating the pathways involving methanol oxidation, formaldehyde assimilation and dissimilation in different natural methylotrophs is essential for subsequent genetic engineering modification, and is more conducive to the construction of novel non-natural methylotrophs. This review discusses the current status of research on methanol metabolic pathways in methylotrophs, and presents recent advances and challenges in natural and synthetic methylotrophs and their applications in methanol bioconversion.

    参考文献
    [1] OLAH GA. Beyond oil and gas: the methanol economy[J]. Angewandte Chemie International Edition, 2005, 44(18): 2636-2639.
    [2] COTTON CA, CLAASSENS NJ, BENITO- VAQUERIZO S, BAR-EVEN A. Renewable methanol and formate as microbial feedstocks[J]. Current Opinion in Biotechnology, 2020, 62: 168-180.
    [3] ZHANG WM, SONG M, YANG Q, DAI ZX, ZHANG SJ, XIN FX, DONG WL, MA JF, JIANG M. Current advance in bioconversion of methanol to chemicals[J]. Biotechnology for Biofuels, 2018, 11(1): 1-11.
    [4] 张卉, 袁姚梦, 张翀, 杨松, 邢新会. 合成甲基营养细胞工厂同化甲醇的研究进展及未来展望[J]. 合成生物学, 2021, 2(2): 222-233. ZHANG H, YUAN YM, ZHANG C, YANG S, XING XH. Research progresses and future prospects of synthetic methylotrophic cell factory for methanol assimilation[J]. Synthetic Biology Journal, 2021, 2(2): 222-233 (in Chinese).
    [5] 陶雨萱, 张尚杰, 景艺文, 信丰学, 董维亮, 周杰, 蒋羽佳, 章文明, 姜岷. 甲基营养型大肠杆菌构建策略的研究进展[J]. 化工进展, 2021, 40(7): 3932-3941. TAO YX, ZHANG SJ, JING YW, XIN FX, DONG WL, ZHOU J, JIANG YJ, ZHANG WM, JIANG M. Recent advances in the construction strategy of methylotrophic Escherichia coli[J]. Chemical Industry and Engineering Progress, 2021, 40(7): 3932-3941 (in Chinese).
    [6] 高教琪, 周雍进. 甲醇生物转化的机遇与挑战[J]. 合成生物学, 2020, 1(2): 158-173. GAO JQ, ZHOU YJ. Advances in methanol bio-transformation[J]. Synthetic Biology Journal, 2020, 1(2): 158-173 (in Chinese).
    [7] MATSUSHITA K, ARENTS JC, BADER R, YAMADA M, ADACHI O, POSTMA PW. Escherichia coli is unable to produce pyrroloquinoline quinone (PQQ)[J]. Microbiology, 1997, 143(10): 3149-3156.
    [8] CHISTOSERDOVA L, CHEN SW, LAPIDUS A, LIDSTROM ME. Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view[J]. Journal of Bacteriology, 2003, 185(10): 2980-2987.
    [9] VELTEROP JS, SELLINK E, MEULENBERG JJ, DAVID S, BULDER I, POSTMA PW. Synthesis of pyrroloquinoline quinone in vivo and in vitro and detection of an intermediate in the biosynthetic pathway[J]. Journal of Bacteriology, 1995, 177(17): 5088-5098.
    [10] SHEEHAN MC, BAILEY CJ, DOWDS BA, McCONNELL DJ. A new alcohol dehydrogenase, reactive towards methanol, from Bacillus stearothermophilus[J]. Biochemical Journal, 1988, 252(3): 661-666.
    [11] KROG A, HEGGESET TMB, MÜLLER JEN, KUPPER CE, SCHNEIDER O, VORHOLT JA, ELLINGSEN TE, BRAUTASET T. Methylotrophic Bacillus methanolicus encodes two chromosomal and one plasmid born NAD+ dependent methanol dehydrogenase paralogs with different catalytic and biochemical properties[J]. PLoS One, 2013, 8(3): e59188.
    [12] OCHSNER AM, MÜLLER JEN, MORA CA, VORHOLT JA. In vitro activation of NAD-dependent alcohol dehydrogenases by Nudix hydrolases is more widespread than assumed[J]. FEBS Letters, 2014, 588(17): 2993-2999.
    [13] WITTHOFF S, SCHMITZ K, NIEDENFÜHR S, NÖH K, NOACK S, BOTT M, MARIENHAGEN J. Metabolic engineering of Corynebacterium glutamicum for methanol metabolism[J]. Applied and Environmental Microbiology, 2015, 81(6): 2215-2225.
    [14] MÜLLER JEN, MEYER F, LITSANOV B, KIEFER P, POTTHOFF E, HEUX S, QUAX WJ, WENDISCH VF, BRAUTASET T, PORTAIS JC, VORHOLT JA. Engineering Escherichia coli for methanol conversion[J]. Metabolic Engineering, 2015, 28: 190-201.
    [15] LIMTONG S, SRISUK N, YONGMANITCHAI W, YURIMOTO H, NAKASE T. Ogataea chonburiensis sp. nov. and Ogataea nakhonphanomensis sp. nov., thermotolerant, methylotrophic yeast species isolated in Thailand, and transfer of Pichia siamensis and Pichia thermomethanolica to the genus Ogataea[J]. International Journal of Systematic and Evolutionary Microbiology, 2008, 58(1): 302-307.
    [16] YURIMOTO H, KATO N, SAKAI Y. Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism[J]. The Chemical Record, 2005, 5(6): 367-375.
    [17] KATO N, YURIMOTO H, THAUER RK. The physiological role of the ribulose monophosphate pathway in bacteria and Archaea[J]. Bioscience, Biotechnology, and Biochemistry, 2006, 70(1): 10-21.
    [18] DALTON H. The biochemistry of methylotrophs[J]. Trends in Biochemical Sciences, 1983, 8(9): 342-343.
    [19] STOLZENBERGER J, LINDNER SN, WENDISCH VF. The methylotrophic Bacillus methanolicus MGA3 possesses two distinct fructose 1,6-bisphosphate aldolases[J]. Microbiology, 2013, 159(Pt_8): 1770-1781.
    [20] VUILLEUMIER S, CHISTOSERDOVA L, LEE MC, BRINGEL F, LAJUS A, ZHOU Y, GOURION B, BARBE V, CHANG J, CRUVEILLER S, DOSSAT C, GILLETT W, GRUFFAZ C, HAUGEN E, HOURCADE E, LEVY R, MANGENOT S, MULLER E, NADALIG T, PAGNI M, et al. Methylobacterium genome sequences: a reference blueprint to investigate microbial metabolism of C1 compounds from natural and industrial sources[J]. PLoS One, 2009, 4(5): e5584.
    [21] CROWTHER GJ, KOSÁLY G, LIDSTROM ME. Formate as the main branch point for methylotrophic metabolism in Methylobacterium extorquens AM1[J]. Journal of Bacteriology, 2008, 190(14): 5057-5062.
    [22] KAWAGUCHI K, YURIMOTO H, OKU M, SAKAI Y. Yeast methylotrophy and autophagy in a methanol-oscillating environment on growing Arabidopsis thaliana leaves[J]. PLoS One, 2011, 6(9): e25257.
    [23] CEREGHINO JL, CREGG JM. Heterologous protein expression in the methylotrophic yeast Pichia pastoris[J]. FEMS Microbiology Reviews, 2000, 24(1): 45-66.
    [24] ZHAO LS, CHANG WC, XIAO YL, LIU HW, LIU PH. Methylerythritol phosphate pathway of isoprenoid biosynthesis[J]. Annual Review of Biochemistry, 2013, 82: 497-530.
    [25] NAGAI H, MASUDA A, TOYA Y, MATSUDA F. Shimizu H. Metabolic engineering of mevalonate- producing Escherichia coli strains based on thermodynamic analysis[J]. Metabolic Engineering, 2018, 47: 1-9.
    [26] SONNTAG F, KRONER C, LUBUTA P, PEYRAUD R, HORST A, BUCHHAUPT M, SCHRADER J. Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid α-humulene from methanol[J]. Metabolic Engineering, 2015, 32: 82-94.
    [27] ALI SHAH A, HASAN F, HAMEED A, AHMED S. Biological degradation of plastics: a comprehensive review[J]. Biotechnology Advances, 2008, 26(3): 246-265.
    [28] GAO X, CHEN JC, WU Q, CHEN GQ. Polyhydroxyalkanoates as a source of chemicals, polymers, and biofuels[J]. Current Opinion in Biotechnology, 2011, 22(6): 768-774.
    [29] ORITA I, NISHIKAWA K, NAKAMURA S, FUKUI T. Biosynthesis of polyhydroxyalkanoate copolymers from methanol by Methylobacterium extorquens AM1 and the engineered strains under cobalt-deficient conditions[J]. Applied Microbiology and Biotechnology, 2014, 98(8): 3715-3725.
    [30] SUZUKI T, YAMANE T, SHIMIZU S. Kinetics and effect of nitrogen source feeding on production of poly-β-hydroxybutyric acid by fed-batch culture[J]. Applied Microbiology and Biotechnology, 1986, 24(5): 366-369.
    [31] van DIEN SJ, MARX CJ, O՚BRIEN BN, LIDSTROM ME. Genetic characterization of the carotenoid biosynthetic pathway in Methylobacterium extorquens AM1 andIsolation of a Colorless Mutant[J]. Applied and Environmental Microbiology, 2003, 69(12): 7563-7566.
    [32] LIANG WF. Biosensor-assisted transcriptional regulator engineering for Methylobacterium extorquens AM1 to improve mevalonate synthesis by increasing the acetyl-CoA supply[J]. Metabolic Engineering, 2017, 39: 159-168.
    [33] DAI ZX. Metabolic construction strategies for direct methanol utilization in Saccharomyces cerevisiae[J]. Bioresource Technology, 2017, 245: 1407-1412.
    [34] KUENZ A, GALLENMÜLLER Y, WILLKE T, VORLOP KD. Microbial production of itaconic acid: developing a stable platform for high product concentrations[J]. Applied Microbiology and Biotechnology, 2012, 96(5): 1209-1216.
    [35] SONNTAG F, BUCHHAUPT M, SCHRADER J. Thioesterases for ethylmalonyl-CoA pathway der[52] GUO F, DAI ZX, PENG WF, ZHANG SJ, ZHOU J, MA JF, DONG WL, XIN FX, ZHANG WM, JIANG M. Metabolic engineering of Pichia pastoris for malic acid production from methanol[J]. Biotechnology and Bioengineering, 2021, 118(1): 357-371.
    [53] ERB TJ, FUCHS G, ALBER BE. (2S)-Methylsuccinyl- CoA dehydrogenase closes the ethylmalonyl-CoA pathway for acetyl-CoA assimilation[J]. Molecular Microbiology, 2009, 73(6): 992-1008.
    [54] HU B, LIDSTROM ME. Metabolic engineering of Methylobacterium extorquens AM1 for 1-butanol production[J]. Biotechnology for Biofuels, 2014, 7(1): 1-10.
    [55] HU B, YANG YM, BECK DAC, WANG QW, CHEN WJ, YANG J, LIDSTROM ME, YANG S. Comprehensive molecular characterization of Methylobacterium extorquens AM1 adapted for 1-butanol tolerance[J]. Biotechnology for Biofuels, 2016, 9(1): 1-14.
    [56] FILLET S, ADRIO JL. Microbial production of fatty alcohols[J]. World Journal of Microbiology and Biotechnology, 2016, 32(9): 1-10.
    [57] MOTOYAMA H, ANAZAWA H, KATSUMATA R, ARAKI K, TESHIBA S. Amino acid production from methanol byMethylobacillus glycogenes Mutants: isolation of l-glutamic acid hyper-producing mutants from M. glycogenes strains, and deriⅶation of l-threonine and l-lysine-producing mutants from them[J]. Bioscience, Biotechnology, and Biochemistry, 1993, 57(1): 82-87.
    [58] MOTOYAMA H, YANO H, TERASAKI Y, ANAZAWA H. Overproduction of l-lysine from methanol by Methylobacillus glycogenes derivatives carrying a plasmid with a mutated dapA gene[J]. Applied and Environmental Microbiology, 2001, 67(7): 3064-3070.
    [59] HANSON RS, DILLINGHAM R, OLSON P, LEE GH, CUE D, SCHENDEL FJ, BREMMON C, FLIEKINGER MC. Production of l-lysine and some other amino acids by mutants of B. methanolicus[M]// Microbial Growth on C1 Compounds. Dordrecht: Springer Netherlands, 1996: 227-236.
    [60] GUNJI Y, YASUEDA H. Enhancement of l-lysine production in methylotroph Methylophilus methylotrophus by introducing a mutant LysE exporter[J]. Journal of Biotechnology, 2006, 127(1): 1-13.
    [61] SIRIROTE P, YAMANE T, SHIMIZU S. Production of l-serine from methanol and glycine by resting cells of a methylotroph under automatically controlled conditions[J]. Journal of Fermentation Technology, 1986, 64(5): 389-396.
    [62] HAGISHITA T, YOSHIDA T, IZUMI Y, MITSUNAGA T. Efficient l-serine production from methanol and Glycine by resting cells of Methylobacterium sp. strain MN43[J]. Bioscience, Biotechnology, and Biochemistry, 1996, 60(10): 1604-1607.
    [63] SCHENDEL FJ, BREMMON CE, FLICKINGER MC, GUETTLER M, HANSON RS. l-lysine production at 50 degrees C by mutants of a newly isolated and characterized methylotrophic Bacillus sp.[J]. Applied and Environmental Microbiology, 1990, 56(4): 963-970.
    [64] AOKI R, WADA M, TAKESUE N, TANAKA K, YOKOTA A. Enhanced glutamic acid production by a H+-ATPase-defective mutant of Corynebacterium glutamicum[J]. Bioscience, Biotechnology, and Biochemistry, 2005, 69(8): 1466-1472.
    [65] ARFMAN N, DIJKHUIZEN L, KIRCHHOF G, LUDWIG W, SCHLEIFER KH, BULYGINA ES, CHUMAKOV KM, GOVORUKHINA NI, TROTSENKO YA, WHITE D, SHARP RJ. Bacillus methanolicus sp. nov., a new species of thermotolerant, methanol-utilizing, endospore-forming bacteria[J]. International Journal of Systematic Bacteriology, 1992, 42(3): 439-445.
    [66] BENNETT RK. Expression of heterologous non-oxidative pentose phosphate pathway from Bacillus methanolicus and phosphoglucose isomerase deletion improves methanol assimilation and metabolite production by a synthetic Escherichia coli methylotroph[J]. Metabolic Engineering, 2018, 45: 75-85.
    [67] WHITAKER WB. Engineering the biological conversion of methanol to specialty chemicals in Escherichia coli[J]. Metabolic Engineering, 2017, 39: 49-59.
    [68] YU H, LIAO JC. A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds[J]. Nature Communications, 2018, 165‒174: 3992.
    [69] ZHANG WM, ZHANG T, SONG M, DAI ZX, ZHANG SJ, XIN FX, DONG WL, MA JF, JIANG M. Metabolic engineering of Escherichia coli for high yield production of succinic acid driven by methanol[J]. ACS Synthetic Biology, 2018, 7(12): 2803-2811.
    [70] PRICE JV, CHEN L, WHITAKER WB, PAPOUTSAKIS E, CHEN W. Scaffoldless engineered enzyme assembly for enhanced methanol utilization[J]. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(45): 12691-12696.
    [71] WANG C, REN J, ZHOU LB, LI ZD, CHEN L, ZENG AP. An aldolase-catalyzed new metabolic pathway for the assimilation of formaldehyde and methanol to synthesize 2-keto-4-hydroxybutyrate and 1, 3-propanediol in Escherichia coli[J]. ACS Synthetic Biology, 2019, 8(11): 2483-2493.
    [72] TUYISHIME P. Engineering Corynebacterium glutamicum for methanol-dependent growth and glutamate production[J]. Metabolic Engineering, 2018, 49: 220-231.
    [73] LESSMEIER L, PFEIFENSCHNEIDER J, CARNICER M, HEUX S, PORTAIS JC, WENDISCH VF. Production of carbon-13-labeled cadaverine by engineered Corynebacterium glutamicum using carbon-13-labeled methanol as co-substrate[J]. Applied Microbiology and Biotechnology, 2015, 99(23): 10163-10176.
    [74] CUI LY, LIANG WF, ZHU WL, SUN MY, ZHANG C, XING XH.. Medium redesign for stable cultivation and high production of mevalonate by recombinant Methtylobacterium extorquens AM1 with mevalonate synthetic pathway[J]. Biochemical Engineering Journal, 2017, 119: 67-73.
    [75] SIEGEL JB, LEE SMITH A, POUST S, WARGACKI AJ, BAR-EVEN A, LOUW C, SHEN BW, EIBEN CB, TRAN HM, NOOR E, GALLAHER JL, BALE J, YOSHIKUNI Y, GELB MH, KEASLING JD, STODDARD BL, LIDSTROM ME, BAKER D. Computational protein design enables a novel one-carbon assimilation pathway[J]. Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(12): 3704-3709.
    [76] LU XY, LIU YW, YANG YQ, WANG SS, WANG Q, WANG XY, YAN ZH, CHENG J, LIU C, YANG X, LUO H, YANG S, GOU JR, YE LZ, LU LN, ZHANG ZD, GUO Y, NIE Y, LIN JP, LI S, et al. Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design[J]. Nature Communications, 2019, 10: 1378.
    [77] YANG JG, SUN SS, MEN Y, ZENG Y, ZHU YM, SUN YX, MA YH. Transformation of formaldehyde into functional sugars via multi-enzyme stepwise cascade catalysis[J]. Catalysis Science & Technology, 2017, 7(16): 3459-3463.
    [78] ZHANG SJ, GUO F, YANG Q, JIANG YJ, YANG SH, MA JF, XIN FX, HASUNUMA T, KONDO A, ZHANG WM, JIANG M. Improving methanol assimilation in Yarrowia lipolytica via systematic metabolic engineering combined with compartmentalization[J]. Green Chemistry, 2023, 25(1): 183-195.
    [79] ROTH TB, WOOLSTON BM, STEPHANOPOULOS G, LIU DR. Phage-assisted evolution of Bacillus methanolicus methanol dehydrogenase 2[J]. ACS Synthetic Biology, 2019, 8(4): 796-806.
    [80] CELIK E, CALIK P, OLIVER SG. Metabolic flux analysis for recombinant protein production by Pichia pastoris using dual carbon sources: effects of methanol feeding rate[J]. Biotechnology and Bioengineering, 2010, 105(2): 317-329. DOI: 10.1002/bit.22543. PMID: 19777584.
    引证文献
    网友评论
    网友评论
    分享到微博
    发 布
引用本文

刘康,乔杨怡,张尚杰,郭峰,马江锋,信丰学,章文明,姜岷. 甲醇生物转化合成化学品的研究进展[J]. 生物工程学报, 2023, 39(6): 2430-2448

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2022-12-15
  • 录用日期:2023-03-07
  • 在线发布日期: 2023-06-20
  • 出版日期: 2023-06-25
文章二维码
您是第5997902位访问者
生物工程学报 ® 2025 版权所有

通信地址：中国科学院微生物研究所    邮编：100101

电话：010-64807509   E-mail：cjb@im.ac.cn

技术支持：北京勤云科技发展有限公司