Application of artificial scaffold systems in microbial metabolic engineering
Open accessAbstract
In nature, metabolic pathways are often organized into complex structures such as multienzyme complexes, enzyme molecular scaffolds, or reaction microcompartments. These structures help facilitate multi-step metabolic reactions. However, engineered metabolic pathways in microbial cell factories do not possess inherent metabolic regulatory mechanisms, which can result in metabolic imbalance. Taking inspiration from nature, scientists have successfully developed synthetic scaffolds to enhance the performance of engineered metabolic pathways in microbial cell factories. By recruiting enzymes, synthetic scaffolds facilitate the formation of multi-enzyme complexes, leading to the modulation of enzyme spatial distribution, increased enzyme activity, and a reduction in the loss of intermediate products and the toxicity associated with harmful intermediates within cells. In recent years, scaffolds based on proteins, nucleic acids, and various organelles have been developed and employed to facilitate multiple metabolic pathways. Despite varying degrees of success, synthetic scaffolds still encounter numerous challenges. The objective of this review is to provide a comprehensive introduction to these synthetic scaffolds and discuss their latest research advancements and challenges.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Synthetic scaffolds or protein interaction domains can enhance metabolic flux by positioning enzymes in close proximity and improving substrate channelling within engineered pathways.
“Recent advances in synthetic biology have further explored the spatial organisation of pathway enzymes through synthetic scaffolds or protein interaction domains, aiming to enhance metabolic flux by positioning enzymes in close proximity and thereby improving substrate channelling within engineered pathways [153].”
From Cyanobacteria as a Photosynthetic Chassis for Metabolic Pathway Engineering with Heterologous Gene Expression (2026) · cites this paper as [153]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Accurate prediction of protein structures and interactions using a 3-track network
Baek, M., DiMaio, F., Anishchenko, I., Dauparas, J., Ovchinnikov, S., Lee, G. R., Wang, J., Cong, Q., Kinch, L. N., Schaeffer, R. D., et al. (2021) · doi:10.1101/2021.06.14.448402 · Cited by 5,542 · see citing works
Breaking the Code of DNA Binding Specificity of TAL-Type III Effectors
Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A., & Bonas, U. (2009) · Science · doi:10.1126/science.1178811 · Cited by 2,707 · see citing works
Watson, J. L., Juergens, D., Bennett, N. R., Trippe, B. L., Yim, J., Eisenach, H. E., Ahern, W., Borst, A. J., Ragotte, R. J., Milles, L. F., et al. (2022) · doi:10.1101/2022.12.09.519842 · Cited by 2,369 · see citing works
De novo design of protein structure and function with RFdiffusion
Watson, J. L., Juergens, D., Bennett, N. R., Trippe, B. L., Yim, J., Eisenach, H. E., Ahern, W., Borst, A. J., Ragotte, R. J., Milles, L. F., et al. (2023) · Nature · doi:10.1038/s41586-023-06415-8 · Cited by 2,325 · see citing works
PCNA, the Maestro of the Replication Fork
Moldovan, G.-L., Pfander, B., & Jentsch, S. (2007) · Cell · doi:10.1016/j.cell.2007.05.003 · Cited by 1,796 · see citing works
Structures of Gram-Negative Cell Walls and Their Derived Membrane Vesicles
Beveridge, T. J. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.16.4725-4733.1999 · Cited by 1,533 · see citing works
Synthetic protein scaffolds provide modular control over metabolic flux
Dueber, J. E., Wu, G. C., Malmirchegini, G. R., Moon, T. S., Petzold, C. J., Ullal, A. V., Prather, K. L. J., & Keasling, J. D. (2009) · Nature Biotechnology · doi:10.1038/nbt.1557 · Cited by 1,242 · see citing works
A guide to genome engineering with programmable nucleases
Kim, S., & Kim, J. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3686 · Cited by 1,162 · see citing works
AKAP signalling complexes: focal points in space and time
Wong, W., & Scott, J. D. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1527 · Cited by 1,073 · see citing works
<i>Xanthomonas</i> AvrBs3 Family-Type III Effectors: Discovery and Function
Boch, J., & Bonas, U. (2010) · Annual Review of Phytopathology · doi:10.1146/annurev-phyto-080508-081936 · Cited by 978 · see citing works
Engineering complex synthetic transcriptional programs with CRISPR RNA scaffolds
Zalatan, J. G., Lee, M. E., Almeida, R., Gilbert, L. A., Whitehead, E. H., La Russa, M., Tsai, J. C., Weissman, J. S., Dueber, J. E., Qi, L. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.11.052 · Cited by 938 · see citing works
The trRosetta server for fast and accurate protein structure prediction
Du, Z., Su, H. L., Wang, W., Ye, L., Wei, H., Peng, Z., Anishchenko, I. V., Baker, D. A., & Yang, J. (2021) · Nature Protocols · doi:10.1038/s41596-021-00628-9 · Cited by 716 · see citing works
Organization of Intracellular Reactions with Rationally Designed RNA Assemblies
Delebecque, C. J., Lindner, A. B., Silver, P. A., & Aldaye, F. A. (2011) · Science · doi:10.1126/science.1206938 · Cited by 634 · see citing works
A microbial supply chain for production of the anti-cancer drug vinblastine
Zhang, J., Hansen, L. G., Gudich, O., Viehrig, K., Lassen, L. M. M., Schrübbers, L. C., Adhikari, K. B., Rubaszka, P., Carrasquer-Alvarez, E., Chen, L., et al. (2022) · Nature · doi:10.1038/s41586-022-05157-3 · Cited by 481 · see citing works
A Specificity Map for the PDZ Domain Family
Tonikian, R., Zhang, Y., Sazinsky, S. L., Currell, B., Yeh, J.-H., Reva, B., Held, H. A., Appleton, B. A., Evangelista, M., Wu, Y., et al. (2008) · PLoS Biology · doi:10.1371/journal.pbio.0060239 · Cited by 476 · see citing works
Cellulosomes: bacterial nanomachines for dismantling plant polysaccharides
Artzi, L., Bayer, E. A., & Moraïs, S. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.164 · Cited by 476 · see citing works
Schlessinger, J. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90087-6 · Cited by 454 · see citing works
Enzyme clustering accelerates processing of intermediates through metabolic channeling
Castellana, M., Wilson, M. Z., Xu, Y., Joshi, P., Cristea, I. M., Rabinowitz, J. D., Gitai, Z., & Wingreen, N. S. (2014) · Nature Biotechnology · doi:10.1038/nbt.3018 · Cited by 447 · see citing works
Kerfeld, C. A., Aussignargues, C., Zarzycki, J., Cai, F., & Sutter, M. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2018.10 · Cited by 445 · see citing works
Biosynthesis of medicinal tropane alkaloids in yeast
Srinivasan, P., & Smolke, C. D. (2020) · Nature · doi:10.1038/s41586-020-2650-9 · Cited by 375 · see citing works
Engineering the spatial organization of metabolic enzymes: mimicking nature's synergy
Conrado, R. J., Varner, J. D., & DeLisa, M. P. (2008) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2008.07.006 · Cited by 372 · see citing works
Evolution and Diversity of Assembly-Line Polyketide Synthases
Nivina, A., Yuet, K. P., Hsu, J., & Khosla, C. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00525 · Cited by 331 · see citing works
Protein–protein interactions: PDZ domain networks
Fanning, A. S., & Anderson, J. M. (1996) · Current Biology · doi:10.1016/s0960-9822(96)00737-3 · Cited by 300 · see citing works
Modular enzyme assembly for enhanced cascade biocatalysis and metabolic flux
Kang, W., Ma, T., Liu, M., Qu, J., Liu, Z., Zhang, H., Shi, B., Fu, S., Ma, J., Lai, L. T. F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12247-w · Cited by 297 · see citing works
Use of modular, synthetic scaffolds for improved production of glucaric acid in engineered E. coli
Moon, T. S., Dueber, J. E., Shiue, E., & Prather, K. L. J. (2010) · Metabolic Engineering · doi:10.1016/j.ymben.2010.01.003 · Cited by 296 · see citing works
DNA-guided assembly of biosynthetic pathways promotes improved catalytic efficiency
Conrado, R. J., Wu, G. C., Boock, J. T., Xu, H., Chen, S. Y., Lebar, T., Turnšek, J., Tomšič, N., Avbelj, M., Gaber, R., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr888 · Cited by 274 · see citing works
Zhou, Y. J., Buijs, N. A. A., Zhu, Z., Gómez, D. O., Boonsombuti, A., Siewers, V., & Nielsen, J. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b07394 · Cited by 210 · see citing works
Dynamic control of signaling by modular adaptor proteins
Pawson, T. J. (2007) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2007.02.013 · Cited by 205 · see citing works
Lawrence, A. D., Frank, S., Newnham, S. E., Lee, M. J., Brown, I. R., Xue, W., Rowe, M. L., Mulvihill, D. P., Prentice, M. B., Howard, M. J., et al. (2014) · ACS Synthetic Biology · doi:10.1021/sb4001118 · Cited by 187 · see citing works
Sachdeva, G., Garg, A., Godding, D., Way, J. C., & Silver, P. A. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku617 · Cited by 156 · see citing works
Genetic engineering of modular PKSs: from combinatorial biosynthesis to synthetic biology
Weissman, K. J. (2015) · Natural Product Reports · doi:10.1039/c5np00109a · Cited by 156 · see citing works
De novo biosynthesis of rubusoside and rebaudiosides in engineered yeasts
Xu, Y., Wang, X., Zhang, C., Zhou, X., Xu, X., Han, L., Lv, X., Liu, Y., Liu, S., Li, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30826-2 · Cited by 146 · see citing works
Self-citationBiochemical and Structural Insights into Bacterial Organelle Form and Biogenesis
Parsons, J. B., Sriramulu, D. D., Deery, E. C., Leech, H. K., Brindley, A. A., Heldt, D., Frank, S., Smales, C. M., Lünsdorf, H., Rambach, A., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709214200 · Cited by 141 · see citing works
Petit, E., LaTouf, W. G., Coppi, M. V., Warnick, T. A., Currie, D. H., Romashko, I., Deshpande, S., Haas, K., Alvelo-Maurosa, J. G., Wardman, C., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054337 · Cited by 139 · see citing works
Bacterial Nanobioreactors–Directing Enzyme Packaging into Bacterial Outer Membrane Vesicles
Alves, N. J., Turner, K. B., Daniele, M. A.-A., Oh, E., Medintz, I. L., & Walper, S. A. (2015) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5b08811 · Cited by 135 · see citing works
Lumsden, J., & Coggins, J. R. (1977) · Biochemical Journal · doi:10.1042/bj1610599 · Cited by 132 · see citing works
Structure of D-AKAP2:PKA RI Complex: Insights into AKAP Specificity and Selectivity
Sarma, G. N., Kinderman, F. S., Kim, C., von Daake, S., Chen, L., Wang, B., & Taylor, S. S. (2010) · Structure · doi:10.1016/j.str.2009.12.012 · Cited by 127 · see citing works
Scaffoldless engineered enzyme assembly for enhanced methanol utilization
Price, J. V., Chen, L., Whitaker, W. B., Papoutsakis, E. T., & Chen, W. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1601797113 · Cited by 127 · see citing works
Shi, Y., Wang, D., Li, R., Huang, L., Dai, Z., & Zhang, X. (2021) · Metabolic Engineering · doi:10.1016/j.ymben.2021.06.002 · Cited by 118 · see citing works
Park, S. Y., Eun, H., Lee, M. H., & Lee, S. Y. (2022) · Nature Catalysis · doi:10.1038/s41929-022-00820-4 · Cited by 110 · see citing works
Proteins of bacteriophage phi6
Sinclair, J. F., Tzagoloff, A., Levine, D., & Mindich, L. (1975) · Journal of Virology · doi:10.1128/jvi.16.3.685-695.1975 · Cited by 102 · see citing works
Liu, F., Banta, S. A., & Chen, W. (2013) · Chemical Communications · doi:10.1039/c3cc40454d · Cited by 101 · see citing works
Sato, K., & Hamada, M. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad186 · Cited by 101 · see citing works
Redirecting Photosynthetic Reducing Power toward Bioactive Natural Product Synthesis
Nielsen, A. Z., Ziersen, B., Jensen, K., Lassen, L. M. M., Olsen, C. E., Møller, B. L., & Jensen, P. E. (2013) · ACS Synthetic Biology · doi:10.1021/sb300128r · Cited by 100 · see citing works
Synthetic Multienzyme Complexes, Catalytic Nanomachineries for Cascade Biosynthesis In Vivo
Qu, J., Cao, S., Wei, Q., Zhang, H., Wang, R. Y., Kang, W., Ma, T., Zhang, L. N., Liu, T., Au, S. W., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b03631 · Cited by 98 · see citing works
Lee, M. J., Brown, I. R., Juodeikis, R., Frank, S., & Warren, M. J. (2016) · Metabolic Engineering · doi:10.1016/j.ymben.2016.02.007 · Cited by 96 · see citing works
Synthetic scaffolds for pathway enhancement
Siu, K., Chen, R. P., Sun, Q. H., Chen, L., Tsai, S., & Chen, W. (2015) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2015.08.009 · Cited by 95 · see citing works
Synthetic Protein Scaffolds for Biosynthetic Pathway Colocalization on Lipid Droplet Membranes
Lin, J., Zhu, J., & Wheeldon, I. R. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.7b00041 · Cited by 92 · see citing works
Butyrate production in engineered Escherichia coli with synthetic scaffolds
Baek, J., Mazumdar, S., Lee, S., Jung, M.-Y., Lim, J. H., Seo, S. W., Jung, G., & Oh, M. (2013) · Biotechnology and Bioengineering · doi:10.1002/bit.24925 · Cited by 90 · see citing works
Liu, Y., Zhu, Y., Ma, W., Shin, H., Li, J., Liu, L., Du, G., & Chen, J. (2014) · Metabolic Engineering · doi:10.1016/j.ymben.2014.04.004 · Cited by 90 · see citing works
Self-citationMolecular Assembly of P450 with Ferredoxin and Ferredoxin Reductase by Fusion to PCNA
Hirakawa, H., & Nagamune, T. (2010) · ChemBioChem · doi:10.1002/cbic.201000226 · Cited by 87 · see citing works
Positional Assembly of Enzymes on Bacterial Outer Membrane Vesicles for Cascade Reactions
Park, M., Sun, Q. H., Liu, F., DeLisa, M. P., & Chen, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097103 · Cited by 82 · see citing works
Improved Production of l -Threonine in Escherichia coli by Use of a DNA Scaffold System
Lee, J. H., Jung, S., Bui, L. M., Kang, K. H., Song, J., & Kim, S. C. (2012) · Applied and Environmental Microbiology · doi:10.1128/aem.02578-12 · Cited by 81 · see citing works
Gao, X., Yang, S., Zhao, C., Ren, Y., & Wei, D. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201405016 · Cited by 78 · see citing works
Biomolecular scaffolds for enhanced signaling and catalytic efficiency
Chen, R., Chen, Q., Kim, H., Siu, K., Sun, Q. H., Tsai, S., & Chen, W. (2013) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2013.11.007 · Cited by 76 · see citing works
Affibody Scaffolds Improve Sesquiterpene Production in Saccharomyces cerevisiae
Tippmann, S., Anfelt, J., David, F., Rand, J. M., Siewers, V., Uhlén, M., Nielsen, J., & Hudson, E. P. (2016) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00109 · Cited by 76 · see citing works
Reconfigurable asymmetric protein assemblies through implicit negative design
Sahtoe, D. D., Praetorius, F., Courbet, A., Hsia, Y., Wicky, B. I. M., Edman, N. I., Miller, L. M., Timmermans, B. J. R., Decarreau, J. A., Morris, H. M., et al. (2022) · Science · doi:10.1126/science.abj7662 · Cited by 72 · see citing works
Strategies and perspectives of assembling multi-enzyme systems
Wang, S., Zhang, Y., Ren, H., Wang, Y., Jiang, W., & Fang, B. (2017) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2017.1303803 · Cited by 69 · see citing works
Production of Rainbow Colorants by Metabolically Engineered Escherichia coli
Yang, D., Park, S. Y., & Lee, S. Y. (2021) · Advanced Science · doi:10.1002/advs.202100743 · Cited by 69 · see citing works
Designing and using RNA scaffolds to assemble proteins in vivo
Delebecque, C. J., Silver, P. A., & Lindner, A. B. (2012) · Nature Protocols · doi:10.1038/nprot.2012.102 · Cited by 61 · see citing works
CipA and CipB as Scaffolds To Organize Proteins into Crystalline Inclusions
Wang, Y., Heermann, R., & Jung, K. (2017) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00323 · Cited by 61 · see citing works
Biosynthesis of mushroom-derived type II ganoderic acids by engineered yeast
Yuan, W., Jiang, C., Wang, Q., Fang, Y., Wang, J., Wang, M., & Xiao, H. (2022) · Nature Communications · doi:10.1038/s41467-022-35500-1 · Cited by 61 · see citing works
Metabolic pathway assembly using docking domains from type I cis-AT polyketide synthases
Sun, X., Yuan, Y.-J., Chen, Q., Nie, S., Guo, J., Ou, Z., Huang, M., Deng, Z., Liu, T., & Ma, T. (2022) · Nature Communications · doi:10.1038/s41467-022-33272-2 · Cited by 58 · see citing works
Building Spatial Synthetic Biology with Compartments, Scaffolds, and CommunitiesPreprint
Polka, J., Hays, S. G., & Silver, P. A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a024018 · Cited by 51 · see citing works
AlphaFold predicts the most complex protein knot and composite protein knots
Brems, M. A., Runkel, R., Yeates, T. O., & Virnau, P. (2022) · Protein Science · doi:10.1002/pro.4380 · Cited by 50 · see citing works
Wei, Q., He, S., Qu, J. Y., & Xia, J. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00476 · Cited by 49 · see citing works
Organizing Enzymes on Self‐Assembled Protein Cages for Cascade Reactions
Kang, W., Ma, X., Kakarla, D., Zhang, H., Fang, Y., Chen, B., Zhu, K., Zheng, D., Wu, Z., Li, B., et al. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202214001 · Cited by 48 · see citing works
Synthetic Lipid-Containing Scaffolds Enhance Production by Colocalizing Enzymes
Myhrvold, C., Polka, J., & Silver, P. A. (2016) · ACS Synthetic Biology · doi:10.1021/acssynbio.6b00141 · Cited by 45 · see citing works
Protein scaffolds: A tool for multi-enzyme assembly
Gad, S., & Ayakar, S. R. (2021) · Biotechnology Reports · doi:10.1016/j.btre.2021.e00670 · Cited by 45 · see citing works
Phạm, V. D., Lee, S. H., Park, S. J., & Hong, S. H. (2015) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2015.04.028 · Cited by 43 · see citing works
Rahman, M. Z., Sung, B. H., Yi, J., Bui, L. M., Lee, J. H., & Kim, S. C. (2014) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2014.10.014 · Cited by 43 · see citing works
Research progress and the biotechnological applications of multienzyme complex
Jiang, Y., Zhang, X., Yuan, H., Huang, D., Wang, R., Liu, H., & Wang, T. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-021-11121-4 · Cited by 41 · see citing works
Zhao, C., Gao, X., Liu, X.-B., Wang, Y., Yang, S., Wang, F., & Ren, Y. (2016) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6b00650 · Cited by 40 · see citing works
Ji, D., Li, J., Xu, F., Ren, Y., & Wang, Y. (2021) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00606 · Cited by 40 · see citing works
Self-citationSynthetic Protein Scaffolds for Improving R-(−)-Linalool Production in Escherichia coli
Wu, J., Wang, X., Xiao, L., Wang, F., Zhang, Y., & Li, X. (2021) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c01101 · Cited by 40 · see citing works
Zhou, Y., Dong, J., & Wang, Q. (2023) · NPG Asia Materials · doi:10.1038/s41427-023-00470-3 · Cited by 40 · see citing works
Pothoulakis, G., Nguyen, M. T. A., & Andersen, E. S. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac470 · Cited by 38 · see citing works
de Jesus, M. P. R. H., Nielsen, A. Z., Mellor, S. B., Matthes, A., Burow, M., Robinson, C., & Jensen, P. E. (2017) · Metabolic Engineering · doi:10.1016/j.ymben.2017.09.014 · Cited by 37 · see citing works
Plasmid-directed assembly of the lipid-containing membrane of bacteriophage phi 6
Johnson, M. D., & Mindich, L. (1994) · Journal of Bacteriology · doi:10.1128/jb.176.13.4124-4132.1994 · Cited by 34 · see citing works
Enhanced itaconic acid production by self‐assembly of two biosynthetic enzymes in Escherichia coli
Yang, Z., Gao, X., Xie, H., Wang, F., Ren, Y., & Wei, D. (2016) · Biotechnology and Bioengineering · doi:10.1002/bit.26081 · Cited by 34 · see citing works
Li, T., Chen, X., Cai, Y., & Dai, J. (2018) · Metabolic Engineering · doi:10.1016/j.ymben.2018.07.006 · Cited by 31 · see citing works
Ivanov, Y. D., Taldaev, A., Лисица, А. В., Ponomarenko, E. A., & Archakov, A. I. (2022) · Molecules · doi:10.3390/molecules27041386 · Cited by 30 · see citing works
Reifenrath, M., Oreb, M., Boles, E., & Tripp, J. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00241 · Cited by 29 · see citing works
CRISPR/Cas-directed programmable assembly of multi-enzyme complexes
Lim, S., Kim, J., Kim, Y., Xu, D., & Clark, D. S. (2020) · Chemical Communications · doi:10.1039/d0cc01174f · Cited by 28 · see citing works
Morphogenesis of bacteriophage φ6. A presumptive viral membrane precursor
Stitt, B. L., & Mindich, L. (1983) · Virology · doi:10.1016/0042-6822(83)90157-5 · Cited by 27 · see citing works
Somasundaram, S., Jeong, J., Ganesh, I., Kim, T., & Hong, S. H. (2020) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-019-0269-1 · Cited by 27 · see citing works
Luo, Z., Pan, F., Zhu, Y., Du, S., Yan, Y., Wang, R., Li, S., & Xu, H. L. (2022) · ACS Synthetic Biology · doi:10.1021/acssynbio.2c00157 · Cited by 26 · see citing works
Synthetic Scaffold Systems for Increasing the Efficiency of Metabolic Pathways in Microorganisms
Geraldi, A., Khairunnisa, F., Farah, N., Bui, L. M., & Rahman, Z. U. (2021) · Biology · doi:10.3390/biology10030216 · Cited by 24 · see citing works
Exploiting dCas9 fusion proteins for dynamic assembly of synthetic metabolons
Berckman, E. A., & Chen, W. (2019) · Chemical Communications · doi:10.1039/c9cc04002a · Cited by 23 · see citing works
Self-assembly systems to troubleshoot metabolic engineering challenges
Chen, Z., Wu, T., Yu, S., Li, M., Fan, X., & Huo, Y. (2023) · Trends in biotechnology · doi:10.1016/j.tibtech.2023.06.009 · Cited by 23 · see citing works
Kim, S., Bae, S., & Hahn, J. (2016) · Scientific Reports · doi:10.1038/srep24145 · Cited by 21 · see citing works
Assembly of TALE-based DNA scaffold for the enhancement of exogenous multi-enzymatic pathway
Xie, S., Qiu, X., Zhu, L., Zhu, C., Liu, C., Wu, X., Zhu, L., & Zhang, D. (2019) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2019.03.008 · Cited by 21 · see citing works
Enzyme Assembly for Compartmentalized Metabolic Flux Control
Lv, X., Cui, S., Gu, Y. M., Li, J., Du, G., & Liu, L. (2020) · Metabolites · doi:10.3390/metabo10040125 · Cited by 21 · see citing works
Self-citationSpatial organization of heterologous metabolic system in vivo based on TALE
Zhu, L., Qiu, X., Zhu, L., Wu, X., Zhang, Y., Zhu, Q., Fan, D., Zhu, C., & Zhang, D. (2016) · Scientific Reports · doi:10.1038/srep26065 · Cited by 20 · see citing works
The structure of a polyketide synthase bimodule core
Tittes, Y. U., Herbst, D. A., Martin, S. F. X., Muñoz-Hernández, H., Jakob, R. P., & Maier, T. (2022) · Science Advances · doi:10.1126/sciadv.abo6918 · Cited by 20 · see citing works
Synthetic Multienzyme Assemblies for Natural Product Biosynthesis
Liu, M., Wang, Y., Jiang, H., Han, Y., & Xia, J. (2023) · ChemBioChem · doi:10.1002/cbic.202200518 · Cited by 17 · see citing works
Metabolic enzyme clustering by coiled coils improves the biosynthesis of resveratrol and mevalonate
Fink, T., Stevović, B., Verwaal, R., Roubos, J. A., Gaber, R., Benčina, M., Jerala, R., & Gradišar, H. (2020) · AMB Express · doi:10.1186/s13568-020-01031-5 · Cited by 16 · see citing works
Multienzyme Assembly on Caveolar Membranes In Cellulo
Wei, Q., Wang, Y., Liu, Z., Liu, M., Cao, S., Jiang, H., & Xia, J. (2022) · ACS Catalysis · doi:10.1021/acscatal.2c01906 · Cited by 16 · see citing works
Phạm, V. D., Somasundaram, S., Lee, S. H., Park, S. J., & Hong, S. H. (2015) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-015-1948-9 · Cited by 15 · see citing works
A modular approach for dCas9-mediated enzyme cascading via orthogonal bioconjugation
Berckman, E. A., & Chen, W. (2020) · Chemical Communications · doi:10.1039/d0cc04196c · Cited by 15 · see citing works
Wang, L., Sun, Y. R., Lv, D., Liu, B., Guan, Y., & Yu, D. (2020) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-10990-5 · Cited by 15 · see citing works
Sarin, L. P., Hirvonen, J. J., Laurinmäki, P., Butcher, S. J., Bamford, D. H., & Poranen, M. M. (2012) · Journal of Virology · doi:10.1128/jvi.00172-12 · Cited by 11 · see citing works
Impact of the Synthetic Scaffold Strategy on the Metabolic Pathway Engineering
Tran, K.-N. T., Kumaravel, A., & Hong, S. H. (2023) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-022-0350-z · Cited by 8 · see citing works
Prediction of scaffold proteins based on protein interaction and domain architectures
Oh, K., & Yi, G. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-1079-5 · Cited by 6 · see citing works
RNA Scaffold: Designed to Co-localize Enzymes
ZJU_China Team (iGEM 2012), & Chen, M. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2730-2_9 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cascade Catalytic Nanozymes: Design, Classification, and Biomedical Applications
Wang, S., Wang, L., Yan, X., & Jiang, B. (2025) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.5c09544 · Cited by 46 · see citing works
Biosynthesis of Edible Terpenoids: Hosts and Applications
Wang, M., Zhang, Z., Liu, X., Liu, Z., & Liu, R. (2025) · Foods · doi:10.3390/foods14040673 · Cited by 12 · see citing works
Ezeako, E. C., Nwiloh, B. I., Odo, M. C., & Ozougwu, V. E. (2025) · Biochemical Engineering Journal · doi:10.1016/j.bej.2025.109777 · Cited by 14 · see citing works
Design of a diblock-based membraneless organelle system for metabolic process control
Ke, J., Wan, L., Chen, M., Lv, Y., Liu, Y., Zhu, Y., Zhang, W., & Mu, W. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.160239 · Cited by 8 · see citing works
Recent advances in bioinspired multienzyme engineering for food applications
Chen, X., Chen, Y., Tang, D., Li, M., Lu, Y., Cao, Y. H., Zhao, Q., Jiang, S., Liu, W., & Jiang, L. (2024) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2024.104840 · Cited by 7 · see citing works
Engineering microbial cell factories for the production of lycopene: Advances and perspectives
Huang, G., Lan, Y., Duan, C., & Yan, G. (2025) · Food Research International · doi:10.1016/j.foodres.2025.118270 · Cited by 7 · see citing works
Argonaute-driven programmable multi-enzyme complex assembly on ribosomal RNA scaffolds
Yan, G., Li, X., Yu, X., Zhai, C., Li, W., & Ma, L. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.143974 · Cited by 4 · see citing works
Compatibility engineering of synthetic metabolic pathways in microbial cell factories
Zhang, H., Jia, H., & Li, C. (2025) · Chemical Engineering Science · doi:10.1016/j.ces.2025.122623 · Cited by 3 · see citing works
Gong, H., Meng, Y., Sun, Y., Yang, B., Wang, L., Lin, X., Han, L., Guo, J., Zhu, X., Pepłowski, Ł., et al. (2025) · Advanced Functional Materials · doi:10.1002/adfm.202514761 · Cited by 3 · see citing works
Xu, S., Gao, S., Qi, X., Kan, G., Jayaweer, J. A. A. S., & An, Y. (2025) · Bioresource Technology · doi:10.1016/j.biortech.2025.132540 · Cited by 3 · see citing works
Wang, Y., Wu, J., Wang, N., Zhang, B., Dong, J., Liu, Y., Zhao, M., & Fu, B. (2025) · Food Research International · doi:10.1016/j.foodres.2025.118250 · Cited by 2 · see citing works
Walshe, J., & Saha, S. K. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48060638 · Cited by 1 · see citing works
“…in synthetic biology have further explored the spatial organisation of pathway enzymes through synthetic scaffolds or protein interaction domains, aiming to enhance metabolic flux by positioning enzymes in close proximity and thereby improving substrate channelling within engineered pathways [153].”
Kirdhanthu, S. S., Nandu, S. S., Laxmi, B., & Viswanath, B. (2025) · Next research. · doi:10.1016/j.nexres.2025.101146
Ashbya gossypii : From Riboflavin Workhorse to a Next-Generation Cell Factory
Jiménez, A., López-Rubio, M., Martín‐González, J., Hernández‐Gómez, A., & Buey, R. M. (2026) · Critical Insights in Biotechnology · doi:10.1080/29932238.2026.2673683
Spore-Forming Probiotic-Embedded Biomaterials for Targeted Gut Microplastic Biodegradation
Nicolas, G. M., Yuan, T., Rukmana, A., Zhang, Z., Qiao, R., & Ma, S. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.6c00183
Fatima, S. W., & Alam, S. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1921701
- Authors
- Liu, N., Dong, W., Yang, H., Li, J.-H., & Chiu, T.-Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Chiu, Tsan-Yu
- Venue
- Frontiers in Bioengineering and Biotechnology
- Publisher
- Frontiers Media SA
- Published
- 2023-12-22
- Volume
- 11
- Pages
- 1328141-1328141
- ISSN
- 2296-4185 (ISSN-L)
- PMC
- PMC10771841
- OpenAlex
- W4390111565
- Cited by
- 16
- References
- 104
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 1
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme Catalysis and Immobilization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- synthetic scaffolds, microbial metabolic engineering, metabolic pathway engineering, multienzyme complex, enzyme scaffolds, metabolic imbalance, protein scaffolds, microbial cell factories
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
