Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products
Source abstract
Abstract
Abstract Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal gene regulatory circuits (GRCs) at the single‐cell level. Utilizing this platform, the expression intensity and timing of 30 transcription factor‐promoter combinations derived from two representative fungal GRCs, using the model fungus Aspergillus nidulans are determined. As a proof of concept, the selected GRC combination is utilized to successfully refactor the biosynthetic pathways of bioactive molecules, precisely control their production, and activate the expression of the silenced biosynthetic gene clusters (BGCs). This study provides insights into microbial gene regulation and highlights the potential of platform in fungal synthetic biology applications and the discovery of novel natural products.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Microbial Metabolic Engineering and Bioproduction · Microbial Natural Products and Biosynthesis · Gene Regulatory Network Analysis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
State Key Laboratory of Mycology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. China
Medical School University of Chinese Academy of Sciences Beijing 100049 P. R. China
Center for Quantitative Biology Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 P. R. China
The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of Physics Peking University Beijing 100871 P. R. China
CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 P. R. China
State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences Beijing 100101 P. R. China
Wenzhou Institute University of Chinese Academy of Sciences Wenzhou Zhejiang 325001 P. R. China
Funding
National Natural Science Foundation of China · Key Research Program of Frontier Science, Chinese Academy of Sciences
References (91)
Show source-provided references
1. 10.1038/s41467-020-20122-210.1038/s41467-020-20122-2 ↗
2. 10.1038/s41467-020-19092-210.1038/s41467-020-19092-2 ↗
3. 10.1042/BST2019034910.1042/BST20190349 ↗
4. 10.1021/bp970132510.1021/bp9701325 ↗
5. 10.1021/acssynbio.3c0012210.1021/acssynbio.3c00122 ↗
6. 10.1016/j.biotechadv.2023.10817710.1016/j.biotechadv.2023.108177 ↗
7. 10.1080/07388551.2023.217674010.1080/07388551.2023.2176740 ↗
8. 10.1016/j.copbio.2016.04.01610.1016/j.copbio.2016.04.016 ↗
9. 10.1016/j.tibtech.2020.12.00410.1016/j.tibtech.2020.12.004 ↗
10. 10.1016/j.cbpa.2015.08.01010.1016/j.cbpa.2015.08.010 ↗
11. 10.1038/nature0464010.1038/nature04640 ↗
12. 10.1038/nature1205110.1038/nature12051 ↗
13. 10.1038/s41586-020-2650-910.1038/s41586-020-2650-9 ↗
14. 10.1038/s41586-019-0978-910.1038/s41586-019-0978-9 ↗
15. 10.1126/science.abh404910.1126/science.abh4049 ↗
16. 10.1038/s41929-022-00775-610.1038/s41929-022-00775-6 ↗
17. 10.1016/j.tibtech.2022.01.00210.1016/j.tibtech.2022.01.002 ↗
18. 10.15252/msb.2015654010.15252/msb.20156540 ↗
19. 10.1038/nmeth.251510.1038/nmeth.2515 ↗
20. 10.1038/nrmicro.2015.2410.1038/nrmicro.2015.24 ↗
21. 10.1016/j.synbio.2017.09.00310.1016/j.synbio.2017.09.003 ↗
22. 10.1002/biot.20180042110.1002/biot.201800421 ↗
23. 10.1016/j.biotechadv.2021.10769510.1016/j.biotechadv.2021.107695 ↗
24. 10.1038/s41467-024-46314-810.1038/s41467-024-46314-8 ↗
25. 10.1007/s00253-023-12660-810.1007/s00253-023-12660-8 ↗
26. 10.1016/j.tibtech.2005.06.00210.1016/j.tibtech.2005.06.002 ↗
27. 10.1016/j.biotechadv.2020.10755110.1016/j.biotechadv.2020.107551 ↗
28. 10.1038/s41467-023-40027-010.1038/s41467-023-40027-0 ↗
29. 10.1146/annurev.phyto.43.040204.14021410.1146/annurev.phyto.43.040204.140214 ↗
30. 10.1038/s41579-018-0121-110.1038/s41579-018-0121-1 ↗
31. 10.1016/j.bbrc.2023.02.06110.1016/j.bbrc.2023.02.061 ↗
32. 10.1007/s11427-022-2214-210.1007/s11427-022-2214-2 ↗
33. 10.1038/nature0434110.1038/nature04341 ↗
34. 10.3390/ijms2216870910.3390/ijms22168709 ↗
35. 10.1038/s41467-017-00063-z10.1038/s41467-017-00063-z ↗
36. 10.1073/pnas.151102711210.1073/pnas.1511027112 ↗
37. 10.1038/nmeth.365910.1038/nmeth.3659 ↗
38. 10.1007/s11427-022-2175-010.1007/s11427-022-2175-0 ↗
39. 10.1038/srep4220010.1038/srep42200 ↗
40. 10.1101/gr.265595.12010.1101/gr.265595.120 ↗
41. 10.1038/s41587-020-0480-910.1038/s41587-020-0480-9 ↗
42. 10.1038/s41467-019-11028-910.1038/s41467-019-11028-9 ↗
43. 10.1038/s41586-019-1369-y10.1038/s41586-019-1369-y ↗
44. 10.1038/s41580-022-00466-x10.1038/s41580-022-00466-x ↗
45. 10.1038/s41586-022-05046-910.1038/s41586-022-05046-9 ↗
46. 10.1038/nrm404110.1038/nrm4041 ↗
47. 10.1002/biot.20170017010.1002/biot.201700170 ↗
48. 10.1126/science.122572010.1126/science.1225720 ↗
49. 10.1073/pnas.090316310610.1073/pnas.0903163106 ↗
50. 10.1111/j.1474-9726.2012.00821.x10.1111/j.1474-9726.2012.00821.x ↗
51. 10.1073/pnas.111350510910.1073/pnas.1113505109 ↗
52. 10.1126/science.add763110.1126/science.add7631 ↗
53. 10.1111/mmi.1371110.1111/mmi.13711 ↗
54. 10.1111/mmi.1428110.1111/mmi.14281 ↗
55. 10.3390/jof708060610.3390/jof7080606 ↗
56. 10.1016/S1087-1845(02)00526-110.1016/S1087-1845(02)00526-1 ↗
57. Pal A. K. · Med. Mycol. · 2014 · 52 · 10
58. 10.1080/0265203070154649510.1080/02652030701546495 ↗
59. 10.1111/j.1365-2958.2012.07986.x10.1111/j.1365-2958.2012.07986.x ↗
60. Wang P. · Microbiol. Spectr. · 2022 · 1010.1128/spectrum.00791-21 ↗
61. 10.1186/s40694-018-0049-210.1186/s40694-018-0049-2 ↗
62. 10.1371/journal.pone.001676510.1371/journal.pone.0016765 ↗
63. 10.1007/978-1-4939-9142-6_710.1007/978-1-4939-9142-6_7 ↗
64. 10.1021/acssynbio.8b0048010.1021/acssynbio.8b00480 ↗
65. 10.1021/acssynbio.2c0030710.1021/acssynbio.2c00307 ↗
66. 10.1016/S0040-4039(01)88668-810.1016/S0040-4039(01)88668-8 ↗
67. Steinrauf L. K. · Met. Ions Biol. Syst. · 1985 · 19 · 139
68. 10.1016/j.chembiol.2008.07.01110.1016/j.chembiol.2008.07.011 ↗
69. 10.1073/pnas.182193211610.1073/pnas.1821932116 ↗
70. 10.1021/sb400048b10.1021/sb400048b ↗
71. 10.1126/sciadv.abo609410.1126/sciadv.abo6094 ↗
72. 10.1002/anie.20230425210.1002/anie.202304252 ↗
73. 10.1021/ja103262m10.1021/ja103262m ↗
74. 10.1016/j.tim.2015.02.00510.1016/j.tim.2015.02.005 ↗
75. 10.1002/anie.20221721210.1002/anie.202217212 ↗
76. 10.1039/D0SC06647H10.1039/D0SC06647H ↗
77. 10.1016/j.fgb.2018.08.00110.1016/j.fgb.2018.08.001 ↗
78. 10.1039/C4OB01494D10.1039/C4OB01494D ↗
79. 10.1093/femsre/fuac03910.1093/femsre/fuac039 ↗
80. 10.1371/journal.ppat.100328910.1371/journal.ppat.1003289 ↗
81. 10.1038/ncomms1061010.1038/ncomms10610 ↗
82. 10.1073/pnas.130256611010.1073/pnas.1302566110 ↗
83. 10.1021/acssynbio.6b0001110.1021/acssynbio.6b00011 ↗
84. 10.1038/nrg248410.1038/nrg2484 ↗
85. 10.1038/nrg293410.1038/nrg2934 ↗
86. 10.1038/s41576-019-0150-210.1038/s41576-019-0150-2 ↗
87. 10.1002/anie.20150709710.1002/anie.201507097 ↗
88. 10.1016/j.biotechadv.2008.09.00110.1016/j.biotechadv.2008.09.001 ↗
89. 10.1039/C9MD00054B10.1039/C9MD00054B ↗
90. 10.1007/978-1-61779-564-0_1110.1007/978-1-61779-564-0_11 ↗
91. 10.1007/978-1-62703-122-6_1110.1007/978-1-62703-122-6_11 ↗