Abstract
Metabolic engineering has evolved exponentially due to rapid progress in the development of omics (proteomics, lipidomics and glycomics) technology and synthetic biology toolsets. Particularly, omics technologies, synthetic biology and metabolic engineering are interdependent in terms of principles of technology and their biological applications. In this article, we showcase synthetic biology toolsets currently used for the metabolic engineering of microbes and focus on some of the recent advances in the field. Specifically we have elaborated on recent progress in metabolic engineering, the associated synthetic biology toolsets, microbiome metabolic engineering (MME) and the potential industrial metabolic engineering applications. As a case study for the industrial application of metabolic engineering, we have reviewed the use of synthetic biology toolsets to bioengineer microbes and re-engineer their metabolic pathways for customised industrial applications. Some of the examples included in this article are as follows: (a) metabolic engineering of cyanobacteria, (b) metabolic engineering of Bacillus subtilis and (c) metabolic engineering in synthetic yeast for industrial applications. As a future perspective, this chapter presents a case for the broader use of synthetic biology toolsets across metabolic engineering applications.
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References
Ando H, Lemire S, Pires DP, Lu TK (2015) Engineering modular viral scaffolds for targeted bacterial population editing. Cell Syst 1(3):187–196
Andrianantoandro E, Basu S, Karig DK, Weiss R (2006) Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2(1):2006–0028
Arnold FH (1998) Design by directed evolution. Acc Chem Res 31(3):125–131
Arnold CD, Gerlach D, Stelzer C, Boryń ŁM, Rath M, Stark A (2013) Genome-wide quantitative enhancer activity maps identified by STARR-seq. Science 339(6123):1074–1077
Atalla, Schumann W (2003) Thepst operon of Bacillus subtilis is specifically induced by alkali stress. J Bacteriol 185:5019–5022
Bailey JE (1991) Toward a science of metabolic engineering. Science 252:1668–1675
Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML, Pogliano J, Stotland A, Wolkowicz R, Cutting AS, Doran KS, Salamon P (2013) Bacteriophage adhering to mucus provide a non–host-derived immunity. Proc Natl Acad Sci 110(26):10771–10776
Beaudry AA, Joyce GF (1992) Directed evolution of an RNA enzyme. Science 257(5070):635–641
Bhattarai Y, Williams BB, Battaglioli EJ, Whitaker WR, Till L, Grover M, Linden DR, Akiba Y, Kandimalla KK, Zachos NC, Kaunitz JD (2018) Gut microbiota-produced tryptamine activates an epithelial G-protein-coupled receptor to increase colonic secretion. Cell Host Microbe 23(6):775–785
Boedicker JQ, Chellamuthu P, Tran F, Silva P, El Naggar M (2018) Engineering bacteria for biogenic synthesis of chalcogenide nanomaterials. bioRxiv:266502
Cani PD (2018) Human gut microbiome: hopes, threats and promises. Gut 67(9):1716–1725
Cao M, Gao M, Lopez-Garcia CL, Wu Y, Seetharam AS, Severin AJ, Shao Z (2017) Centromeric DNA facilitates nonconventional yeast genetic engineering. ACS Synth Biol 6:1545–1553
Capecchi MR (1989) Altering the genome by homologous recombination. Science 244(4910):1288–1292
Chandrasegaran S, Carroll D (2016) Origins of programmable nucleases for genome engineering. J Mol Biol 428(5):963–989
Chankhamjon P, Javdan B, Lopez J Hull R, Chatterjee S, Donia MS (2019) Systematic mapping of drug metabolism by the human gut microbiome. bioRxiv, p 538215
Chen Z, Guo L, Zhang Y, Walzem RL, Pendergast JS, Printz RL, Morris LC, Matafonova E, Stien X, Kang L, Coulon D (2014) Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest 124(8):3391–3406
Christian M, Cermak T, Doyle EL, Schmidt C, Zhang F, Hummel A, Bogdanove AJ, Voytas DF (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761
Cohen SN, Chang AC, Boyer HW, Helling RB (1973) Construction of biologically functional bacterial plasmids in vitro. Proc Natl Acad Sci 70(11):3240–3244
Cooper CJ, Khan Mirzaei M, Nilsson AS (2016) Adapting drug approval pathways for bacteriophage-based therapeutics. Front Microbiol 7:1209
Copp JN, Hanson-Manful P, Ackerley DF, Patrick WM (2014) Error-prone PCR and effective generation of gene variant libraries for directed evolution. In: Directed evolution library creation. Springer, New York, NY, pp 3–22
Danino T, Prindle A, Kwong GA, Skalak M, Li H, Allen K, Hasty J, Bhatia SN (2015) Programmable probiotics for detection of cancer in urine. Sci Transl Med 7(289):289ra84
Dedrick RM, Guerrero-Bustamante CA, Garlena RA, Russell DA, Ford K, Harris K, Gilmour KC, Soothill J, Jacobs-Sera D, Schooley RT, Hatfull GF (2019) Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat Med 25(5):730
Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Nat Acad Sci 108(Suppl 1):4554–4561
Din MO, Danino T, Prindle A, Skalak M, Selimkhanov J, Allen K, Julio E, Atolia E, Tsimring LS, Bhatia SN, Hasty J (2016) Synchronized cycles of bacterial lysis for in vivo delivery. Nature 536(7614):81
Durrer KE, Allen MS, Von Herbing IH (2017) Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU. PLoS One 12(5):e0176286
Endy D (2005) Foundations for engineering biology. Nature 438(7067):449
Esvelt KM, Carlson JC, Liu DR (2011) A system for the continuous directed evolution of biomolecules. Nature 472(7344):499
Gilbert LA, Horlbeck MA, Adamson B, Villalta JE, Chen Y, Whitehead EH, Guimaraes C, Panning B, Ploegh HL, Bassik MC, Qi LS, Kampmann M, Weissman JS (2014) Genome-scale CRISPR-mediated control of gene repression and activation. Cell 159:647–661
Grice EA, Segre JA (2012) The human microbiome: our second genome. Annu Rev Genomics Hum Genet 13:151–170
Hafez M, Hausner G (2012) Homing endonucleases: DNA scissors on a mission. Genome 55(8):553–569
Hassan JO, Curtiss R (1994) Development and evaluation of an experimental vaccination program using a live avirulent Salmonella typhimurium strain to protect immunized chickens against challenge with homologous and heterologous Salmonella serotypes. Infect Immun 62(12):5519–5527
Heijnen JJ, Verheijen PJ (2013) Parameter identification of in vivo kinetic models: limitations and challenges. Biotechnol J 8:768–775
Hess GT, Frésard L, Han K, Lee CH, Li A, Cimprich KA, Montgomery SB, Bassik MC (2016) Directed evolution using dCas9-targeted somatic hypermutation in mammalian cells. Nat Methods 13(12):1036
Ho CL, Tan HQ, Chua KJ, Kang A, Lim KH, Ling KL, Yew WS, Lee YS, Thiery JP, Chang MW (2018) Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nat Biomed Eng 2(1):27
Hsu BB, Gibson TE, Yeliseyev V, Liu Q, Bry L, Silver PA, Gerber GK (2018) Bacteriophages dynamically modulate the gut microbiota and metabolome. BioRxiv, p 454579
Hwang IY, Koh E, Wong A, March JC, Bentley WE, Lee YS, Chang MW (2017) Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models. Nat Commun 8:15028
Integrative, H.M.P (2019) The Integrative human microbiome project. Nature 569(7758):641
Iravani S, Varma RS (2019) Biofactories: engineered nanoparticles via genetically engineered organisms. Green Chem 21:4583–4603
Jackson DA, Symons RH, Berg P (1972) Biochemical method for inserting new genetic information into DNA of simian virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc Natl Acad Sci 69(10):2904–2909
Jakociunas T, Bonde I, Herrgard M, Harrison SJ, Kristensen M, Pedersen LE, Jensen MK, Keasling JD (2015) Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae. Metab Eng 28:213–222
Jeffrey C, Shenoy V, Verma A, Aquino V, Kumar A, Liang Z, Li Q, Katovich M, Raizada M (2016) Genetically modified probiotics for oral delivery of angiotensin-(1-7) confers protection against pulmonary hypertension. Hypertension 68(Suppl 1):A009
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E (2012) A programmable dual-RNA–guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096):816–821
Kang DW, Adams JB, Coleman DM, Pollard EL, Maldonado J, McDonough-Means S, Caporaso JG, Krajmalnik-Brown R (2019) Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota. Sci Rep 9(1):5821
Kim Y-G, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci 93(3):1156–1160
Klein-Marcuschamer D, Ajikumar PK, Stephanopoulos G (2007) Engineering microbial cell factories for biosynthesis of isoprenoid molecules: beyond lycopene. Trends Biotechnol 25:417–424
Konermann S, Brigham MD, Trevino AE, Joung J, Abudayyeh OO, Barcena C, Hsu PD, Habib N, Gootenberg JS, Nishimasu H, Nureki O, Zhang F (2015) Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517:583–588
Kumar RR, Prasad S (2011) Metabolic engineering of bacteria. Indian J Microbiol 51:403–409. https://doi.org/10.1007/s12088-011-0172-8
Kurtz CB, Millet YA, Puurunen MK, Perreault M, Charbonneau MR, Isabella VM, Kotula JW, Antipov E, Dagon Y, Denney WS, Wagner DA (2019) An engineered E. coli Nissle improves hyperammonaemia and survival in mice and shows dose-dependent exposure in healthy humans. Sci Transl Med 11(475):eaau7975
Lederberg J, McCray AT (2001) Ome sweet omics—a genealogical treasury of words. Scientist 15(7):8–8
Lennen RM, Pfleger BF (2013) Microbial production of fatty acid-derived fuels and chemicals. Curr Opin Biotechnol 24:1044–1053
Liu Q, Gao R, Li J, Lin L, Zhao J, Sun W, Tian C (2017) Development of a genome-editing CRISPR/Cas9 system in thermophilic fungal Myceliophthora species and its application to hyper-cellulase production strain engineering. Biotechnol Biofuels 10(1):1
Lynch SV, Pedersen O (2016) The human intestinal microbiome in health and disease. N Engl J Med 375(24):2369–2379
Mansour SL, Thomas KR, Capecchi MR (1988) Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336(6197):348
Maurice CF, Haiser HJ, Turnbaugh PJ (2013) Xenobiotics shape the physiology and gene expression of the active human gut microbiome. Cell 152(1–2):39–50
Mimee M, Citorik RJ, Lu TK (2016) Microbiome therapeutics—advances and challenges. Adv Drug Deliv Rev 105:44–54
Mohamadzadeh M, Pfeiler EA, Brown JB, Zadeh M, Gramarossa M, Managlia E, Bere P, Sarraj B, Khan MW, Pakanati KC, Ansari MJ (2011) Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Nat Acad Sci 108(Suppl 1):4623–4630
Mutalik VK, Guimaraes JC, Cambray G, Mai QA, Christoffersen MJ, Martin L, Yu A, Lam C, Rodriguez C, Bennett G, Keasling JD (2013) Quantitative estimation of activity and quality for collections of functional genetic elements. Nat Methods 10(4):347
Nxumalo Z, Thimiri Govinda Raj DB (2020) Application and challenges of synthetic biology. In: Singh V (ed) Advances in synthetic biology. Springer, Singapore
Ooijevaar RE, Terveer EM, Verspaget HW, Kuijper EJ, Keller JJ (2019) Clinical application and potential of faecal microbiota transplantation. Annu Rev Med 70:335–351
Pires DP, Cleto S, Sillankorva S, Azeredo J, Lu TK (2016) Genetically engineered phages: a review of advances over the last decade. Microbiol Mol Biol Rev 80(3):523–543
Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, Nielsen T, Pons N, Levenez F, Yamada T, Mende DR (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59
Schwartz CM, Hussain MS, Blenner M, Wheeldon I (2016) Synthetic RNA polymerase III promoters facilitate high-efficiency CRISPR-Cas9-mediated genome editing in Yarrowialipolytica. ACS Synth Biol 5:356–359
Sender R, Fuchs S, Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164(3):337–340
Sheth RU, Cabral V, Chen SP, Wang HH (2016) Manipulating bacterial communities by in situ microbiome engineering. Trends Genet 32(4):189–200
Smanski MJ, Zhou H, Claesen J, Shen B, Fischbach MA, Voigt CA (2016) Synthetic biology to access and expand nature's chemical diversity. Nat Rev Microbiol 14(3):135
Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E (2000) Treatment of murine colitis by Lactococcuslactis secreting interleukin-10. Science 289(5483):1352–1355
Stephanopoulos G (2012) Synthetic biology and metabolic engineering. ACS Synth Biol 1(11):514–525
Stephanopoulos G, Vallino J (1991) Network rigidity and metabolic engineering in metabolite overproduction. Science 252:1675–1681
Thimiri Govinda Raj DB, Khan NA (2018) Surface functionalization dependent subcellular localization of superparamagnetic nanoparticle in plasma membrane and endosome. Nano Convergence 5(1):4
Thimiri Govinda Raj DB, Khan NA (2019) Protocol for eukaryotic plasma membrane isolation using superparamagnetic nanoparticles. J Magn Magn Mater 476:628–631
Thimiri Govinda Raj DB, Khan NA, Venkatachalam S, Arumugam S (2019) BacMam system for rapid recombinant protein expression in mammalian cells. In: Turksen K (ed) Stem cell nanotechnology. Methods in molecular biology, vol 2125. Humana, New York, NY
Thimiri Govinda Raj DB, Khan NA, Venkatachalam S, Arumugam S (2020) Efficient nanobiotechnology method for magnetic lysosome enrichment using DMSA-SPMNP 2.0. BioNanoScience 10(2):529–533
Turner NJ (2009) Directed evolution drives the next generation of biocatalysts. Nat Chem Biol 5(8):567
Turner AMW, De La Cruz J, Morris KV (2009) Mobilization-competent lentiviral vector–mediated sustained transcriptional modulation of HIV-1 expression. Mol Ther 17(2):360–368
Vázquez-Baeza Y, Callewaert C, Debelius J, Hyde E, Marotz C, Morton JT, Swafford A, Vrbanac A, Dorrestein PC, Knight R (2018) Impacts of the human gut microbiome on therapeutics. Annu Rev Pharmacol Toxicol 58:253–270
Wang S, Xu M, Wang W, Cao X, Piao M, Khan S, Yan F, Cao H, Wang B (2016) Systematic review: adverse events of faecal microbiota transplantation. PLoS One 11(8):e0161174
Wassef L, Wirawan R, Chikindas M, Breslin PA, Hoffman DJ, Quadro L (2014) β-carotene–producing bacteria residing in the intestine provide vitamin A to mouse tissues in vivo. J Nutr 144(5):608–613
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
Zhang MM, Wong FT, Wang Y, Luo S, Lim YH, Heng E, Yeo WL, Cobb RE, Enghiad B, Ang EL (2017) CRISPR–Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol 13(6):607
Zmora N, Zeevi D, Korem T, Segal E, Elinav E (2016) Taking it personally: personalized utilization of the human microbiome in health and disease. Cell Host Microbe 19(1):12–20
Acknowledgements
This work was supported by Synthetic Biology Centre, Next Generation Health Cluster CSIR Pretoria South Africa. Authors thank all team members in CSIR Synthetic Biology Centre.
Competing Interests: There is no competing interest.
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Naidoo, J. et al. (2020). Recent Advances in Genetic Engineering Tools for Metabolic Engineering. In: Singh, V., Singh, A., Bhargava, P., Joshi, M., Joshi, C. (eds) Engineering of Microbial Biosynthetic Pathways. Springer, Singapore. https://doi.org/10.1007/978-981-15-2604-6_6
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