Abstract
Synthetic biology provides powerful tools and novel strategies for designing and modifying microorganisms to function as cell factories for biomanufacturing, which is a promising approach for realizing chemical production in a green and sustainable manner. Recent advances in genetic component design and genome engineering have enabled significant progresses in the field of synthetic biology chassis that have been developed for enzymes or biochemical production based on synthetic biology strategies, with particular reference to model microorganisms, such as Escherichia coli, Bacillus subtilis, Corynebacterium glutamicum, and Saccharomyces cerevisiae. In this review, strategies for engineering four different functional cellular modules which encompass the total process of biomanufacturing are discussed, including expanding the substrate spectrum for substrate uptake modules, refactoring biosynthetic pathways and dynamic regulation for product synthesis modules, balancing energy and redox modules, and cell membrane and cell wall engineering of product storage and secretion modules. Novel strategies of integrating and coordinating different cellular modules aided by synthetic co-culturing of multiple chassis, artificial intelligence–aided data mining for guiding strain development, and the process for designing automatic chassis development via biofoundry are expected to generate next generations of model microorganism chassis for more efficient biomanufacturing.
Key points
• Engineering of functional cellular modules facilitate next generations of chassis construction.
• Global optimization of biosynthesis can be improved by metabolic models.
• Data-driven and automatic strain development can improve microorganism chassis construction.
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References
Adams BL (2016) The next generation of synthetic biology chassis: moving synthetic biology from the laboratory to the field. ACS Synth Biol 5:1328–1330
Amir A, Babaeipour F, McIntosh DB, Nelson DR, Jun S (2014) Bending forces plastically deform growing bacterial cell walls. Proc Natl Acad Sci U S A 111:5778–5783
Andreozzi S, Miskovic L, Hatzimanikatis V (2016) iSCHRUNK--in silico approach to characterization and reduction of uncertainty in the kinetic models of genome-scale metabolic networks. Metab Eng 33:158–168
Avalos JL, Fink GR, Stephanopoulos G (2013) Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols. Nat Biotechnol 31:335–341
Becker J, Rohles CM, Wittmann C (2018) Metabolically engineered Corynebacterium glutamicum for bio-based production of chemicals, fuels, materials, and healthcare products. Metab Eng 50:122–141
Beites T, Mendes MV (2015) Chassis optimization as a cornerstone for the application of synthetic biology based strategies in microbial secondary metabolism. Front Microbiol 6:906
Bogorad IW, Lin TS, Liao JC (2013) Synthetic non-oxidative glycolysis enables complete carbon conservation. Nature 502:693–697
Brockman IM, Prather KLJ (2015) Dynamic knockdown of E. coli central metabolism for redirecting fluxes of primary metabolites. Metab Eng 28:104–113
Browning DF, Richards KL, Peswani AR, Roobol J, Busby SJW, Robinson C (2017) Escherichia coli “TatExpress” strains super-secrete human growth hormone into the bacterial periplasm by the Tat pathway. Biotechnol Bioeng 114:2828–2836
Calero P, Nikel PI (2019) Chasing bacterial chassis for metabolic engineering: a perspective review from classical to non-traditional microorganisms. Microb Biotechnol 12:98–124
Cao H, van Heel AJ, Ahmed H, Mols M, Kuipers OP (2017) Cell surface engineering of Bacillus subtilis improves production yields of heterologously expressed alpha-amylases. Microb Cell Factories 16:56
Ceroni F, Boo A, Furini S, Gorochowski TE, Borkowski O, Ladak YN, Awan AR, Gilbert C, Stan GB, Ellis T (2018) Burden-driven feedback control of gene expression. Nat Methods 15:387–393
Chao R, Liang J, Tasan I, Si T, Ju L, Zhao H (2017) Fully automated one-step synthesis of single-transcript TALEN pairs using a biological foundry. ACS Synth Biol 6:678–685
Chi H, Wang X, Shao Y, Qin Y, Deng Z, Wang L, Chen S (2019) Engineering and modification of microbial chassis for systems and synthetic biology. Synth Syst Biotechnol 4:25–33
Choi KR, Jang WD, Yang D, Cho JS, Park D, Lee SY (2019) Systems metabolic engineering strategies: integrating systems and synthetic biology with metabolic engineering. Trends Biotechnol 37:817–837
Chubukov V, Gerosa L, Kochanowski K, Sauer U (2014) Coordination of microbial metabolism. Nat Rev Microbiol 12:327–340
Clomburg JM, Crumbley AM, Gonzalez R (2017) Industrial biomanufacturing: the future of chemical production. Science 355:aag0804
Costello Z, Martin HG (2018) A machine learning approach to predict metabolic pathway dynamics from time-series multiomics data. NPJ Syst Biol Appl 4:19
Crook N, Abatemarco J, Sun J, Wagner JM, Schmitz A, Alper HS (2016) In vivo continuous evolution of genes and pathways in yeast. Nat Commun 7:13051
Cui S, Lv X, Wu Y, Li J, Du G, Ledesma-Amaro R, Liu L (2019) Engineering a bfunctional Phr60-Rap60-Spo0A quorum-sensing molecular switch for dynamic fine-tuning of menaquinone-7 synthesis in Bacillus subtilis. ACS Synth Biol 8:1826–1837
Curran KA, Karim AS, Gupta A, Alper HS (2013) Use of expression-enhancing terminators in Saccharomyces cerevisiae to increase mRNA half-life and improve gene expression control for metabolic engineering applications. Metab Eng 19:88–97
Dahl RH, Zhang F, Alonso-Gutierrez J, Baidoo E, Batth TS, Redding-Johanson AM, Petzold CJ, Mukhopadhyay A, Lee TS, Adams PD, Keasling JD (2013) Engineering dynamic pathway regulation using stress-response promoters. Nat Biotechnol 31:1039–1046
Delebecque CJ, Silver PA, Lindner AB (2012) Designing and using RNA scaffolds to assemble proteins in vivo. Nat Protoc 7:1797–1807
Delepine B, Duigou T, Carbonell P, Faulon JL (2018) RetroPath2.0: a retrosynthesis workflow for metabolic engineers. Metab Eng 45:158–170
Ding S, Liao X, Tu W, Wu L, Tian Y, Sun Q, Chen J, Hu QN (2017) EcoSynther: a customized platform to explore the biosynthetic potential in E. coli. ACS Chem Biol 12:2823–2829
Doong SJ, Gupta A, Prather KLJ (2018) Layered dynamic regulation for improving metabolic pathway productivity in Escherichia coli. Proc Natl Acad Sci U S A 115:2964–2969
Dueber JE, Wu GC, Malmirchegini GR, Moon TS, Petzold CJ, Ullal AV, Prather KL, Keasling JD (2009) Synthetic protein scaffolds provide modular control over metabolic flux. Nat Biotechnol 27:753–759
Feng J, Yanyan G, Yan P-F, Song C, Wang Y (2017) Recruiting energy-conserving sucrose utilization pathways for enhanced 2,3-butanediol production in Bacillus subtilis. ACS Sustain Chem Eng 5:11221–11225
Fischer CR, Alper H, Nevoigt E, Jensen KL, Stephanopoulos G (2006) Response to Hammer et al.: tuning genetic control--importance of thorough promoter characterization versus generating promoter diversity. Trends Biotechnol 24:55–56
Garcia S, Trinh CT (2019) Multiobjective strain design: a framework for modular cell engineering. Metab Eng 51:110–120
Gu Y, Lv X, Liu Y, Li J, Du G, Chen J, Rodrigo LA, Liu L (2019) Synthetic redesign of central carbon and redox metabolism for high yield production of N-acetylglucosamine in Bacillus subtilis. Metab Eng 51:59–69
Guo J, Suastegui M, Sakimoto KK, Moody VM, Xiao G, Nocera DG, Joshi NS (2018) Light-driven fine chemical production in yeast biohybrids. Science 362:813–816
Gupta A, Reizman IM, Reisch CR, Prather KL (2017) Dynamic regulation of metabolic flux in engineered bacteria using a pathway-independent quorum-sensing circuit. Nat Biotechnol 35:273–279
Hadicke O, Bettenbrock K, Klamt S (2015) Enforced ATP futile cycling increases specific productivity and yield of anaerobic lactate production in Escherichia coli. Biotechnol Bioeng 112:2195–2199
Hameri T, Boldi MO, Hatzimanikatis V (2019) Statistical inference in ensemble modeling of cellular metabolism. PLoS Comput Biol 15:e1007536
Hammer SK, Avalos JL (2017) Harnessing yeast organelles for metabolic engineering. Nat Chem Biol 13:823–832
Henard CA, Smith HK, Guarnieri MT (2017) Phosphoketolase overexpression increases biomass and lipid yield from methane in an obligate methanotrophic biocatalyst. Metab Eng 41:152–158
Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Le Feuvre R, Friedman DC, Fu X, Gold ND, Herrgard MJ, Holowko MB, Johnson JR, Johnson RA, Keasling JD, Kitney RI, Kondo A, Liu C, Martin VJJ, Menolascina F, Ogino C, Patron NJ, Pavan M, Poh CL, Pretorius IS, Rosser SJ, Scrutton NS, Storch M, Tekotte H, Travnik E, Vickers CE, Yew WS, Yuan Y, Zhao H, Freemont PS (2019) Building a global alliance of biofoundries. Nat Commun 10:2040
Hoffmann SL, Jungmann L, Schiefelbein S, Peyriga L, Cahoreau E, Portais JC, Becker J, Wittmann C (2018) Lysine production from the sugar alcohol mannitol: design of the cell factory Corynebacterium glutamicum SEA-3 through integrated analysis and engineering of metabolic pathway fluxes. Metab Eng 47:475–487
Hollands K, Baron CM, Gibson KJ, Kelly KJ, Krasley EA, Laffend LA, Lauchli RM, Maggio-Hall LA, Nelson MJ, Prasad JC, Ren Y, Rice BA, Rice GH, Rothman SC (2019) Engineering two species of yeast as cell factories for 2′-fucosyllactose. Metab Eng 52:232–242
Hu Y, Zhu Z, Nielsen J, Siewers V (2018) Heterologous transporter expression for improved fatty alcohol secretion in yeast. Metab Eng 45:51–58
Hutchison CA 3rd, Chuang RY, Noskov VN, Assad-Garcia N, Deerinck TJ, Ellisman MH, Gill J, Kannan K, Karas BJ, Ma L, Pelletier JF, Qi ZQ, Richter RA, Strychalski EA, Sun L, Suzuki Y, Tsvetanova B, Wise KS, Smith HO, Glass JI, Merryman C, Gibson DG, Venter JC (2016) Design and synthesis of a minimal bacterial genome. Science 351:aad6253
Jansen MLA, Bracher JM, Papapetridis I, Verhoeven MD, de Bruijn H, de Waal PP, van Maris AJA, Klaassen P, Pronk JT (2017) Saccharomyces cerevisiae strains for second-generation ethanol production: from academic exploration to industrial implementation. FEMS Yeast Res 17. https://academic.oup.com/femsyr
Johnson AO, Gonzalez-Villanueva M, Wong L, Steinbuchel A, Tee KL, Xu P, Wong TS (2017) Design and application of genetically-encoded malonyl-CoA biosensors for metabolic engineering of microbial cell factories. Metab Eng 44:253–264
Jouhten P, Boruta T, Andrejev S, Pereira F, Rocha I, Patil KR (2016) Yeast metabolic chassis designs for diverse biotechnological products. Sci Rep 6:29694
Khodayari A, Maranas CD (2016) A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains. Nat Commun 7:13806
Khodayari A, Zomorrodi AR, Liao JC, Maranas CD (2014) A kinetic model of Escherichia coli core metabolism satisfying multiple sets of mutant flux data. Metab Eng 25:50–62
Klamt S, Muller S, Regensburger G, Zanghellini J (2018) A mathematical framework for yield (vs. rate) optimization in constraint-based modeling and applications in metabolic engineering. Metab Eng 47:153–169
Kracke F, Lai B, Yu S, Kromer JO (2018) Balancing cellular redox metabolism in microbial electrosynthesis and electro fermentation-a chance for metabolic engineering. Metab Eng 45:109–120
Kumar A, Wang L, Ng CY, Maranas CD (2018) Pathway design using de novo steps through uncharted biochemical spaces. Nat Commun 9:184
Kuwahara H, Alazmi M, Cui X, Gao X (2016) MRE: a web tool to suggest foreign enzymes for the biosynthesis pathway design with competing endogenous reactions in mind. Nucleic Acids Res 44:W217–W225
Lau YH, Giessen TW, Altenburg WJ, Silver PA (2018) Prokaryotic nanocompartments form synthetic organelles in a eukaryote. Nat Commun 9:1311
Lee SY, Kim HU (2015) Systems strategies for developing industrial microbial strains. Nat Biotechnol 33:1061–1072
Lee J, Saddler JN, Um Y, Woo HM (2016) Adaptive evolution and metabolic engineering of a cellobiose-and xylose-negative Corynebacterium glutamicum that co-utilizes cellobiose and xylose. Microb Cell Factories 15:20
Lee MJ, Mantell J, Hodgson L, Alibhai D, Fletcher JM, Brown IR, Frank S, Xue WF, Verkade P, Woolfson DN, Warren MJ (2018) Engineered synthetic scaffolds for organizing proteins within the bacterial cytoplasm. Nat Chem Biol 14:142–147
Lee MJ, Palmer DJ, Warren MJ (2019) Biotechnological advances in bacterial microcompartment technology. Trends Biotechnol 37:325–336
Leprince A, van Passel MW, dos Santos VA (2012) Streamlining genomes: toward the generation of simplified and stabilized microbial systems. Curr Opin Biotechnol 23:651–658
Link H, Fuhrer T, Gerosa L, Zamboni N, Sauer U (2015) Real-time metabolome profiling of the metabolic switch between starvation and growth. Nat Methods 12:1091–1097
Liu Y, Link H, Liu L, Du G, Chen J, Sauer U (2016) A dynamic pathway analysis approach reveals a limiting futile cycle in N-acetylglucosamine overproducing Bacillus subtilis. Nat Commun 7:11933
Liu Y, Liu L, Li J, Du G, Chen J (2019) Synthetic biology toolbox and chassis development in Bacillus subtilis. Trends Biotechnol 37:548–562
Lo TM, Chng SH, Teo WS, Cho HS, Chang MW (2016) A two-layer gene circuit for decoupling cell growth from metabolite production. Cell Syst 3:133–143
Lu X, Liu Y, Yang Y, Wang S, Wang Q, Wang X, Yan Z, Cheng J, Liu C, Yang X, Luo H, Yang S, Gou J, Ye L, Lu L, Zhang Z, Guo Y, Nie Y, Lin J, Li S, Tian C, Cai T, Zhuo B, Ma H, Wang W, Ma Y, Liu Y, Li Y, Jiang H (2019) Constructing a synthetic pathway for acetyl-coenzyme A from one-carbon through enzyme design. Nat Commun 10:1378
Majidian P, Kuse J, Tanaka K, Najafi H, Zeinalabedini M, Takenaka S, Yoshida KI (2017) Bacillus subtilis GntR regulation modified to devise artificial transient induction systems. J Gen Appl Microbiol 62:277–285
Marques WL, Mans R, Henderson RK, Marella ER, Horst JT, Hulster E, Poolman B, Daran JM, Pronk JT, Gombert AK, van Maris AJA (2018) Combined engineering of disaccharide transport and phosphorolysis for enhanced ATP yield from sucrose fermentation in Saccharomyces cerevisiae. Metab Eng 45:121–133
Martinez-Garcia E, de Lorenzo V (2016) The quest for the minimal bacterial genome. Curr Opin Biotechnol 42:216–224
Mellor J, Grigoras I, Carbonell P, Faulon JL (2016) Semisupervised gaussian process for automated enzyme search. ACS Synth Biol 5:518–528
Milne N, Luttik MAH, Cueto Rojas HF, Wahl A, van Maris AJA, Pronk JT, Daran JM (2015) Functional expression of a heterologous nickel-dependent, ATP-independent urease in Saccharomyces cerevisiae. Metab Eng 30:130–140
Nielsen J, Keasling JD (2016) Engineering cellular metabolism. Cell 164:1185–1197
Noor E, Cherkaoui S, Sauer U (2019) Biological insights through omics data integration. Curr Opin Syst Biol 15:39–47
Nowroozi FF, Baidoo EE, Ermakov S, Redding-Johanson AM, Batth TS, Petzold CJ, Keasling JD (2014) Metabolic pathway optimization using ribosome binding site variants and combinatorial gene assembly. Appl Microbiol Biotechnol 98:1567–1581
Oyetunde T, Bao FS, Chen JW, Martin HG, Tang YJ (2018) Leveraging knowledge engineering and machine learning for microbial bio-manufacturing. Biotechnol Adv 36:1308–1315
Oyetunde T, Liu D, Martin HG, Tang YJ (2019) Machine learning framework for assessment of microbial factory performance. PLoS One 14:e0210558
Paddon CJ, Keasling JD (2014) Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat Rev Microbiol 12:355–367
Papapetridis I, Verhoeven MD, Wiersma SJ, Goudriaan M, van Maris AJA, Pronk JT (2018) Laboratory evolution for forced glucose-xylose co-consumption enables identification of mutations that improve mixed-sugar fermentation by xylose-fermenting Saccharomyces cerevisiae. FEMS Yeast Res 18. https://academic.oup.com/femsyr
Price JV, Chen L, Whitaker WB, Papoutsakis E, Chen W (2016) Scaffoldless engineered enzyme assembly for enhanced methanol utilization. Proc Natl Acad Sci U S A 113:12691–12696
Qiao K, Wasylenko TM, Zhou K, Xu P, Stephanopoulos G (2017) Lipid production in Yarrowia lipolytica is maximized by engineering cytosolic redox metabolism. Nat Biotechnol 35:173–177
Ravikumar A, Arzumanyan GA, Obadi MKA, Javanpour AA, Liu CC (2018) Scalable, continuous evolution of genes at mutation rates above genomic error thresholds. Cell 175:1946–57.e13
Reuss DR, Altenbuchner J, Mader U, Rath H, Ischebeck T, Sappa PK, Thurmer A, Guerin C, Nicolas P, Steil L, Zhu B, Feussner I, Klumpp S, Daniel R, Commichau FM, Volker U, Stulke J (2017) Large-scale reduction of the Bacillus subtilis genome: consequences for the transcriptional network, resource allocation, and metabolism. Genome Res 27:289–299
Reuss DR, Rath H, Thurmer A, Benda M, Daniel R, Volker U, Mader U, Commichau FM, Stulke J (2018) Changes of DNA topology affect the global transcription landscape and allow rapid growth of a Bacillus subtilis mutant lacking carbon catabolite repression. Metab Eng 45:171–179
Salis HM, Mirsky EA, Voigt CA (2009) Automated design of synthetic ribosome binding sites to control protein expression. Nat Biotechnol 27:946–950
Sanchez BJ, Zhang C, Nilsson A, Lahtvee PJ, Kerkhoven EJ, Nielsen J (2017) Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints. Mol Syst Biol 13:935
Shi H, Bratton BP, Gitai Z, Huang KC (2018) How to build a bacterial cell: mreB as the foreman of E. coli construction. Cell 172:1294–1305
Siu KH, Chen RP, Sun Q, Chen L, Tsai SL, Chen W (2015) Synthetic scaffolds for pathway enhancement. Curr Opin Biotechnol 36:98–106
Skjoedt ML, Snoek T, Kildegaard KR, Arsovska D, Eichenberger M, Goedecke TJ, Rajkumar AS, Zhang J, Kristensen M, Lehka BJ, Siedler S, Borodina I, Jensen MK, Keasling JD (2016) Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast. Nat Chem Biol 12:951–958
Soifer I, Barkai N (2014) Systematic identification of cell size regulators in budding yeast. Mol Syst Biol 10:761
Tai YS, Xiong M, Jambunathan P, Wang J, Wang J, Stapleton C, Zhang K (2016) Engineering nonphosphorylative metabolism to generate lignocellulose-derived products. Nat Chem Biol 12:247–253
Tan Z, Yoon JM, Nielsen DR, Shanks JV, Jarboe LR (2016) Membrane engineering via trans unsaturated fatty acids production improves Escherichia coli robustness and production of biorenewables. Metab Eng 35:105–113
Tashiro Y, Desai SH, Atsumi S (2015) Two-dimensional isobutyl acetate production pathways to improve carbon yield. Nat Commun 6:7488
Thomik T, Wittig I, Choe JY, Boles E, Oreb M (2017) An artificial transport metabolon facilitates improved substrate utilization in yeast. Nat Chem Biol 13:1158–1163
Tian R, Liu Y, Chen J, Li J, Liu L, Du G, Chen J (2019) Synthetic N-terminal coding sequences for fine-tuning gene expression and metabolic engineering in Bacillus subtilis. Metab Eng 55:131–141
Wang P, Yang X, Lin B, Huang J, Tao Y (2017) Cofactor self-sufficient whole-cell biocatalysts for the production of 2-phenylethanol. Metab Eng 44:143–149
Wheeldon I, Minteer SD, Banta S, Barton SC, Atanassov P, Sigman M (2016) Substrate channelling as an approach to cascade reactions. Nat Chem 8:299–309
Wu T, Ye L, Zhao D, Li S, Li Q, Zhang B, Bi C, Zhang X (2017a) Membrane engineering-a novel strategy to enhance the production and accumulation of beta-carotene in Escherichia coli. Metab Eng 43:85–91
Wu Y, Sun X, Lin Y, Shen X, Yang Y, Jain R, Yuan Q, Yan Y (2017b) Establishing a synergetic carbon utilization mechanism for non-catabolic use of glucose in microbial synthesis of trehalose. Metab Eng 39:1–8
Wu Y, Chen T, Liu Y, Lv X, Li J, Du G, Ledesma-Amaro R, Liu L (2018) CRISPRi allows optimal temporal control of N-acetylglucosamine bioproduction by a dynamic coordination of glucose and xylose metabolism in Bacillus subtilis. Metab Eng 49:232–241
Wu W, Zhang Y, Liu D, Chen Z (2019) Efficient mining of natural NADH-utilizing dehydrogenases enables systematic cofactor engineering of lysine synthesis pathway of Corynebacterium glutamicum. Metab Eng 52:77–86
Xu P (2018) Production of chemicals using dynamic control of metabolic fluxes. Curr Opin Biotechnol 53:12–19
Xu P, Li L, Zhang F, Stephanopoulos G, Koffas M (2014) Improving fatty acids production by engineering dynamic pathway regulation and metabolic control. Proc Natl Acad Sci U S A 111:11299–11304
Yang H, Lu X, Hu J, Chen Y, Shen W, Liu L (2018) Boosting secretion of extracellular protein by Escherichia coli via cell wall perturbation. Appl Environ Microbiol 84:e01382–e01318
Zhang H, Wang X (2016) Modular co-culture engineering, a new approach for metabolic engineering. Metab Eng 37:114–121
Zhang L, Xiao WH, Wang Y, Yao MD, Jiang GZ, Zeng BX, Zhang RS, Yuan YJ (2017) Chassis and key enzymes engineering for monoterpenes production. Biotechnol Adv 35:1022–1031
Zhang J, Astorga MA, Gardner JM, Walker ME, Grbin PR, Jiranek V (2018a) Disruption of the cell wall integrity gene ECM33 results in improved fermentation by wine yeast. Metab Eng 45:255–264
Zhang XC, Guo Y, Liu X, Chen XG, Wu Q, Chen GQ (2018b) Engineering cell wall synthesis mechanism for enhanced PHB accumulation in E. coli. Metab Eng 45:32–42
Zhang X, Liu Y, Liu L, Wang M, Li J, Du G, Chen J (2018c) Modular pathway engineering of key carbon-precursor supply-pathways for improved N-acetylneuraminic acid production in Bacillus subtilis. Biotechnol Bioeng 115:2217–2231
Zhao C, Sinumvayo JP, Zhang Y, Li Y (2019) Design and development of a “Y-shaped” microbial consortium capable of simultaneously utilizing biomass sugars for efficient production of butanol. Metab Eng 55:111–119
Zheng H, Ho PY, Jiang M, Tang B, Liu W, Li D, Yu X, Kleckner NE, Amir A, Liu C (2016) Interrogating the Escherichia coli cell cycle by cell dimension perturbations. Proc Natl Acad Sci U S A 113:15000–15005
Zhou K, Qiao K, Edgar S, Stephanopoulos G (2015) Distributing a metabolic pathway among a microbial consortium enhances production of natural products. Nat Biotechnol 33:377–383
Zhou Y, Li G, Dong J, Xing XH, Dai J, Zhang C (2018) MiYA, an efficient machine-learning workflow in conjunction with the YeastFab assembly strategy for combinatorial optimization of heterologous metabolic pathways in Saccharomyces cerevisiae. Metab Eng 47:294–302
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This work is financially supported by the National Key Research and Development Program of China (2018YFA0900300), the National Natural Science Foundation of China (31972854, 31622001, 31671845, 21676119), Key Research and Development Program of Jiangsu Province (BE2019628), and National First-class Discipline Program of Light Industry Technology and Engineering (LITE2018-16).
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YL and LL conceived the topics and wrote the manuscript. AS, JL RL, PX, GD, and LL revised the manuscript. All authors read and approved the manuscript.
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Liu, Y., Su, A., Li, J. et al. Towards next-generation model microorganism chassis for biomanufacturing. Appl Microbiol Biotechnol 104, 9095–9108 (2020). https://doi.org/10.1007/s00253-020-10902-7
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DOI: https://doi.org/10.1007/s00253-020-10902-7