Which option is not typically a product of biosynthesis?

1. Nielsen, J. & Keasling, J. D. Engineering cellular metabolism. Cell 164, 1185–1197 (2016).

   Article  CAS  PubMed  Google Scholar 

2. Kosuri, S. & Church, G. M. Large-scale de novo DNA synthesis: technologies and applications. Nat. Methods 11, 499 (2014).

   Article  CAS  PubMed  PubMed Central  Google Scholar 

3. Heather, J. M. & Chain, B. The sequence of sequencers: the history of sequencing DNA. Genomics 107, 1–8 (2016).

   Article  CAS  PubMed  Google Scholar 

4. Majors, R. E. Historical developments in HPLC and UHPLC column technology: the past 25 years. LCGC North Am. 33, 818–840 (2015).

5. Li, Y. et al. Complete biosynthesis of noscapine and halogenated alkaloids in yeast. Proc. Natl Acad. Sci. USA 115, E3922–E3931 (2018). This paper is the longest known example of a plant biosynthetic pathway reconstructed in a heterologous host, as well as an example of using PNP-producing platforms for producing unnatural PNPs.

   Article  CAS  PubMed  PubMed Central  Google Scholar 

6. Jones, J. A. & Koffas, M. A. G. Optimizing metabolic pathways for the improved production of natural products. Methods Enzym. 575, 179–193 (2016).

   Article  CAS  Google Scholar 

7. Espinosa-Leal, C. A., Puente-Garza, C. A. & García-Lara, S. In vitro plant tissue culture: means for production of biological active compounds. Planta 248, 1–18 (2018).

   Article  CAS  PubMed  PubMed Central  Google Scholar 

8. Lau, W. & Sattely, E. S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349, 1224–1228 (2015).

   Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

9. Jeon, J-E. et al. A pathogen-responsive gene cluster for the production of highly modified fatty acids in tomato. Preprint at https://doi.org/10.1101/408518 (2018).

10. Demain, A. L. Pharmaceutically active secondary metabolites of microorganisms. Appl. Microbiol. Biotechnol. 52, 455–463 (1999).

    Article  CAS  PubMed  Google Scholar 

11. Wendisch, V. F., Jorge, J. M. P., Pérez-García, F. & Sgobba, E. Updates on industrial production of amino acids using Corynebacterium glutamicum. World J. Microbiol. Biotechnol. 32, 105 (2016).

    Article  CAS  PubMed  Google Scholar 

12. Wolf, K. Nonconventional Yeasts in Biotechnology. (Springer, Berlin, 1996).

13. Tsuruta, H. et al. High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS ONE 4, e4489 (2009).

14. Paddon, C. J. & Keasling, J. D. Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat. Rev. Microbiol. 12, 355–367 (2014).

    Article  CAS  PubMed  Google Scholar 

15. Mizrachi, D. et al. A water-soluble DsbB variant that catalyzes disulfide-bond formation in vivo. Nat. Chem. Biol. 13, 1022–1028 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

16. Hammer, S. K. & Avalos, J. L. Harnessing yeast organelles for metabolic engineering. Nat. Chem. Biol. 13, 823–832 (2017).

    Article  CAS  PubMed  Google Scholar 

17. Ajikumar, P. K. et al. Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science 330, 70–74 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

18. Fang, Z., Jones, J. A., Zhou, J. & Koffas, M. A. G. Engineering Escherichia coli co-cultures for production of curcuminoids from glucose. Biotech. J. 13, 1700576 (2018).

    Article  CAS  Google Scholar 

19. Jones, J. A. et al. Complete biosynthesis of anthocyanins using E. coli polycultures. mBio 8, e00621-17 (2017).

20. Minami, H. et al. Microbial production of plant benzylisoquinoline alkaloids. Proc. Natl Acad. Sci. USA 105, 7393–7398 (2008).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

21. Camacho-Zaragoza, J. M. et al. Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol. Microb. Cell Fact. 15, 163 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

22. Trenchard, I. J., Siddiqui, M. S., Thodey, K. & Smolke, C. D. De novo production of the key branch point benzylisoquinoline alkaloid reticuline in yeast. Metab. Eng. 31, 74–83 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

23. DeLoache, W. C. et al. An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose. Nat. Chem. Biol. 11, 465–471 (2015). This paper is an example of applying biosensor-based screening methods to engineering the production of the key BIA branchpoint alkaloid reticuline.

    Article  CAS  PubMed  Google Scholar 

24. Hadadi, N., Hafner, J., Shajkofci, A., Zisaki, A. & Hatzimanikatis, V. ATLAS of biochemistry: A repository of all possible biochemical reactions for synthetic biology and metabolic engineering studies. ACS Synth. Biol. 5, 1155–1166 (2016).

    Article  CAS  PubMed  Google Scholar 

25. Xiao, M. et al. Transcriptome analysis based on next-generation sequencing of non-model plants producing specialized metabolites of biotechnological interest. J. Biotechnol. 166, 122–134 (2013).

    Article  CAS  PubMed  Google Scholar 

26. Brown, S., Clastre, M., Courdavault, V. & O’Connor, S. E. De novo production of the plant-derived alkaloid strictosidine in yeast. Proc. Natl Acad. Sci. USA 112, 3205–3210 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

27. Tai, Y.-S. et al. Engineering nonphosphorylative metabolism to generate lignocellulose-derived products. Nat. Chem. Biol. 12, 247–253 (2016).

    Article  CAS  PubMed  Google Scholar 

28. Siegel, J. B. et al. Computational protein design enables a novel one-carbon assimilation pathway. Proc. Natl Acad. Sci. USA 112, 3704–3709 (2015).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

29. Antonovsky, N. et al. Sugar synthesis from CO2 in Escherichia coli. Cell 166, 115–125 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

30. Xue, Y. & He, Q. Cyanobacteria as cell factories to produce plant secondary metabolites. Front. Bioeng. Biotechnol. 3, 57 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

31. Yishai, O., Lindner, S. N., de la Cruz, J. G., Tenenboim, H. & Bar-Even, A. The formate bio-economy. Curr. Opin. Chem. Biol. 35, 1–9 (2016).

    Article  CAS  PubMed  Google Scholar 

32. Whitaker, W. B. et al. Engineering the biological conversion of methanol to specialty chemicals in Escherichia coli. Metab. Eng. 39, 49–59 (2017).

    Article  CAS  PubMed  Google Scholar 

33. Meadows, A. L. et al. Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature 537, 694–697 (2016).

    Article  ADS  CAS  PubMed  Google Scholar 

34. Rodriguez, A., Kildegaard, K. R., Li, M., Borodina, I. & Nielsen, J. Establishment of a yeast platform strain for production of p-coumaric acid through metabolic engineering of aromatic amino acid biosynthesis. Metab. Eng. 31, 181–188 (2015).

    Article  CAS  PubMed  Google Scholar 

35. Yu, T. et al. Reprogramming yeast metabolism from alcoholic fermentation to lipogenesis. Cell 174, 1549–1558.e14 (2018).

    Article  CAS  PubMed  Google Scholar 

36. Blount, B. A. et al. Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome. Nat. Commun. 9, 1932 (2018). This paper is the first known example of engineering host metabolism through use of inducible chromosome recombination synthetic biology tools.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

37. Caspi, R. et al. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases. Nucleic Acids Res. 42, D459–D471 (2014).

    Article  CAS  PubMed  Google Scholar 

38. Wang, L., Dash, S., Ng, C. Y. & Maranas, C. D. A review of computational tools for design and reconstruction of metabolic pathways. Synth. Syst. Biotechnol. 2, 243–252 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

39. Delépine, B., Duigou, T., Carbonell, P. & Faulon, J.-L. RetroPath2.0: a retrosynthesis workflow for metabolic engineers. Metab. Eng. 45, 158–170 (2018).

    Article  CAS  PubMed  Google Scholar 

40. Fehér, T. et al. Validation of RetroPath, a computer-aided design tool for metabolic pathway engineering. Biotechnol. J. 9, 1446–1457 (2014).

    Article  CAS  PubMed  Google Scholar 

41. Hadadi, N. & Hatzimanikatis, V. Design of computational retrobiosynthesis tools for the design of de novo synthetic pathways. Curr. Opin. Chem. Biol. 28, 99–104 (2015).

    Article  CAS  PubMed  Google Scholar 

42. Casini, A. et al. A pressure test to make 10 molecules in 90 days: external evaluation of methods to engineer biology. J. Am. Chem. Soc. 140, 4302–4316 (2018).

    Article  CAS  PubMed  Google Scholar 

43. Ellerbrock, P., Armanino, N., Ilg, M. K., Webster, R. & Trauner, D. An eight-step synthesis of epicolactone reveals its biosynthetic origin. Nat. Chem. 7, 879–882 (2015).

    Article  CAS  PubMed  Google Scholar 

44. Medema, M. H. et al. Minimum information about a biosynthetic gene cluster. Nat. Chem. Biol. 11, 625–631 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

45. Blin, K. et al. antiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification. Nucleic Acids Res. 45, W36–W41 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

46. Röthlisberger, D. et al. Kemp elimination catalysts by computational enzyme design. Nature 453, 190–195 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

47. Kautsar, S. A., Suarez Duran, H. G., Blin, K., Osbourn, A. & Medema, M. H. plantiSMASH: automated identification, annotation and expression analysis of plant biosynthetic gene clusters. Nucleic Acids Res. 45, W55–W63 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

48. Matasci, N. et al. Data access for the 1,000 Plants (1KP) project. Gigascience 3, 17 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

49. Liu, X. et al. Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches. Nat. Commun. 9, 448 (2018). This paper is an example of the de novo biosynthesis of medicinal alkaloids and demonstrates the application of PNP platform strains for enzyme discovery.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

50. Nagashima, S., Hirotani, M. & Yoshikawa, T. Purification and characterization of UDP-glucuronate: baicalein 7-O-glucuronosyltransferase from Scutellaria baicalensis Georgi. cell suspension cultures. Phytochemistry 53, 533–538 (2000).

    Article  CAS  PubMed  Google Scholar 

51. Farrow, S. C., Hagel, J. M., Beaudoin, G. A. W., Burns, D. C. & Facchini, P. J. Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy. Nat. Chem. Biol. 11, 728–732 (2015).

    Article  CAS  PubMed  Google Scholar 

52. Winzer, T. et al. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein. Science 349, 309–312 (2015).

    Article  ADS  CAS  PubMed  Google Scholar 

53. Galanie, S., Thodey, K., Trenchard, I. J., Filsinger Interrante, M. & Smolke, C. D. Complete biosynthesis of opioids in yeast. Science 349, 1095–1100 (2015). This paper is the first known example of the complete biosynthesis of opioids in yeast and demonstrates the application of PNP platform strains for enzyme discovery.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

54. Caputi, L. et al. Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science 360, 1235–1239 (2018).

    Article  ADS  CAS  PubMed  Google Scholar 

55. Chen, X. et al. A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis. Nat. Chem. Biol. 14, 738–743 (2018).

    Article  CAS  PubMed  Google Scholar 

56. Hsu, T. M. et al. Employing a biochemical protecting group for a sustainable indigo dyeing strategy. Nat. Chem. Biol. 14, 256–261 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

57. Lenz, R. & Zenk, M. H. Acetyl coenzyme A: salutaridinol-7-O-acetyltransferase from papaver somniferum plant cell cultures. The enzyme catalyzing the formation of thebaine in morphine biosynthesis. J. Biol. Chem. 270, 31091–31096 (1995).

    Article  CAS  PubMed  Google Scholar 

58. Barton, D. H. R., Bhakuni, D. S., James, R. & Kirby, G. W. Phenol oxidation and biosynthesis. Part XII. Stereochemical studies related to the biosynthesis of the morphine alkaloids. J. Chem. Soc. C: Organic 0, 128–132 (1967).

59. Qu, Y. et al. Completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast. Proc. Natl Acad. Sci. USA 112, 6224–6229 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

60. Winzer, T. et al. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science 336, 1704–1708 (2012).

    Article  ADS  CAS  PubMed  Google Scholar 

61. Luo, Y., Enghiad, B. & Zhao, H. New tools for reconstruction and heterologous expression of natural product biosynthetic gene clusters. Nat. Prod. Rep. 33, 174–182 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

62. Lee, M. E., DeLoache, W. C., Cervantes, B. & Dueber, J. E. A Highly characterized yeast toolkit for modular, multipart assembly. ACS Synth. Biol. 4, 975–986 (2015).

    Article  CAS  PubMed  Google Scholar 

63. Ryan, O. W., Poddar, S. & Cate, J. H. D. CRISPR–Cas9 genome engineering in Saccharomyces cerevisiae cells. Cold Spring Harb. Protoc. 2016, https://doi.org/10.1101/pdb.prot086827 (2016).

64. Jeschek, M., Gerngross, D. & Panke, S. Rationally reduced libraries for combinatorial pathway optimization minimizing experimental effort. Nat. Commun. 7, 11163 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

65. Li, Y. & Smolke, C. D. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7, 12137 (2016).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

66. Trenchard, I. J. & Smolke, C. D. Engineering strategies for the fermentative production of plant alkaloids in yeast. Metab. Eng. 30, 96–104 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

67. Fossati, E. et al. Reconstitution of a 10-gene pathway for synthesis of the plant alkaloid dihydrosanguinarine in Saccharomyces cerevisiae. Nat. Commun. 5, 3283 (2014).

    Article  CAS  PubMed  Google Scholar 

68. Chao, R., Mishra, S., Si, T. & Zhao, H. Engineering biological systems using automated biofoundries. Metab. Eng. 42, 98–108 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

69. Carbonell, P. et al. An automated design-build-test-learn pipeline for enhanced microbial production of fine chemicals. Commun. Biol. 1, 66 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

70. Thodey, K., Galanie, S. & Smolke, C. D. A microbial biomanufacturing platform for natural and semisynthetic opioids. Nat. Chem. Biol. 10, 837–844 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

71. Dueber, J. E. et al. Synthetic protein scaffolds provide modular control over metabolic flux. Nat. Biotechnol. 27, 753–759 (2009).

    Article  CAS  PubMed  Google Scholar 

72. Sachdeva, G., Garg, A., Godding, D., Way, J. C. & Silver, P. A. In vivo co-localization of enzymes on RNA scaffolds increases metabolic production in a geometrically dependent manner. Nucleic Acids Res. 42, 9493–9503 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

73. Denby, C. M. et al. Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer. Nat. Commun. 9, 965 (2018).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

74. Zeymer, C. & Hilvert, D. Directed evolution of protein catalysts. Annu. Rev. Biochem. 87, 131–157 (2018).

    Article  CAS  PubMed  Google Scholar 

75. Katsuyama, Y., Funa, N., Miyahisa, I. & Horinouchi, S. Synthesis of unnatural flavonoids and stilbenes by exploiting the plant biosynthetic pathway in Escherichia coli. Chem. Biol. 14, 613–621 (2007).

    Article  CAS  PubMed  Google Scholar 

76. Hawkins, K. M. & Smolke, C. D. Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae. Nat. Chem. Biol. 4, 564–573 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

77. Ruff, B. M., Bräse, S. & O’Connor, S. E. Biocatalytic production of tetrahydroisoquinolines. Tetrahedron Lett. 53, 1071–1074 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

78. McCoy, E. & O’Connor, S. E. Directed biosynthesis of alkaloid analogs in the medicinal plant Catharanthus roseus. J. Am. Chem. Soc. 128, 14276–14277 (2006).

    Article  CAS  PubMed  Google Scholar 

79. Valliere, M. A. et al. A cell-free platform for the prenylation of natural products and application to cannabinoid production. Nat. Commun. 10, 565 (2019).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

80. Chemler, J. A., Lim, C. G., Daiss, J. L. & Koffas, M. A. G. A versatile microbial system for biosynthesis of novel polyphenols with altered estrogen receptor binding activity. Chem. Biol. 17, 392–401 (2010).

    Article  CAS  PubMed  Google Scholar 

81. Herrera-Rodriguez, L. N., Khan, F., Robins, K. T. & Meyer, H.-P. Perspectives on biotechnological halogenation Part I: Halogenated products and enzymatic halogenation. Chem. Today 29, 31–33 (2011).

    CAS  Google Scholar 

82. Grewal, P. S., Modavi, C., Russ, Z. N., Harris, N. C. & Dueber, J. E. Bioproduction of a betalain color palette in Saccharomyces cerevisiae. Metab. Eng. 45, 180–188 (2018).

    Article  CAS  PubMed  Google Scholar 

83. Kashkooli, A. B., van der Krol, A., Rabe, P., Dickschat, J. S. & Bouwmeester, H. Substrate promiscuity of enzymes from the sesquiterpene biosynthetic pathways from Artemisia annua and Tanacetum parthenium allows for novel combinatorial sesquiterpene production. Metab. Eng. 54, 12–23 (2019).

    Article  CAS  Google Scholar 

84. Sánchez, C. et al. The biosynthetic gene cluster for the antitumor rebeccamycin: characterization and generation of indolocarbazole derivatives. Chem. Biol. 9, 519–531 (2002).

    Article  PubMed  Google Scholar 

85. Fasan, R., Chen, M. M., Crook, N. C. & Arnold, F. H. Engineered alkane-hydroxylating cytochrome P450BM3 exhibiting nativelike catalytic properties. Angew. Chem. Int. Ed. 46, 8414–8418 (2007).

    Article  CAS  Google Scholar 

86. Payne, J. T., Poor, C. B. & Lewis, J. C. Directed evolution of RebH for site-selective halogenation of large biologically active molecules. Angew. Chem. Int. Ed. Engl. 54, 4226–4230 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

87. Savile, C. K. et al. Biocatalytic asymmetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science 329, 305–309 (2010).

    Article  ADS  CAS  PubMed  Google Scholar 

88. Morita, H. et al. Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase. Proc. Natl Acad. Sci. USA 108, 13504–13509 (2011).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

89. Wanibuchi, K., Morita, H., Noguchi, H. & Abe, I. Enzymatic formation of an aromatic dodecaketide by engineered plant polyketide synthase. Bioorg. Med. Chem. Lett. 21, 2083–2086 (2011).

    Article  CAS  PubMed  Google Scholar 

90. Bhan, N., Cress, B. F., Linhardt, R. J. & Koffas, M. Expanding the chemical space of polyketides through structure-guided mutagenesis of Vitis vinifera stilbene synthase. Biochimie 115, 136–143 (2015).

    Article  CAS  PubMed  Google Scholar 

91. Bhan, N. et al. Enzymatic formation of a resorcylic acid by creating a structure-guided single-point mutation in stilbene synthase. Protein Sci. 24, 167–173 (2015).

    Article  CAS  PubMed  Google Scholar 

92. Ehrenworth, A. M. & Peralta-Yahya, P. Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering. Nat. Chem. Biol. 13, 249–258 (2017).

    Article  CAS  PubMed  Google Scholar 

93. Deb Roy, A., Grüschow, S., Cairns, N. & Goss, R. J. M. Gene expression enabling synthetic diversification of natural products: chemogenetic generation of pacidamycin analogs. J. Am. Chem. Soc. 132, 12243–12245 (2010).

    Article  CAS  PubMed  Google Scholar 

94. Runguphan, W., Qu, X. & O’Connor, S. E. Integrating carbon–halogen bond formation into medicinal plant metabolism. Nature 468, 461–464 (2010). This paper is an example of unnatural PNP production via novel enzyme incorporation into the native plant producer, demonstrating that chlorinated precursor metabolites can transit through a biosynthetic pathway to the terminal products.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

95. Glenn, W. S., Nims, E. & O’Connor, S. E. Reengineering a tryptophan halogenase to preferentially chlorinate a direct alkaloid precursor. J. Am. Chem. Soc. 133, 19346–19349 (2011).

    Article  CAS  PubMed  Google Scholar 

96. Wang, S. et al. Metabolic engineering of Escherichia coli for the biosynthesis of various phenylpropanoid derivatives. Metab. Eng. 29, 153–159 (2015).

    Article  CAS  PubMed  Google Scholar 

97. Townshend, B., Kennedy, A. B., Xiang, J. S. & Smolke, C. D. High-throughput cellular RNA device engineering. Nat. Methods 12, 989–994 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

98. Feng, J. et al. A general strategy to construct small molecule biosensors in eukaryotes. Elife 4, e10606 (2015).

99. Abatemarco, J. et al. RNA-aptamers-in-droplets (RAPID) high-throughput screening for secretory phenotypes. Nat. Commun. 8, 332 (2017).

100. Michener, J. K. & Smolke, C. D. High-throughput enzyme evolution in Saccharomyces cerevisiae using a synthetic RNA switch. Metab. Eng. 14, 306–316 (2012).

     Article  CAS  PubMed  Google Scholar 

101. Raman, S., Rogers, J. K., Taylor, N. D. & Church, G. M. Evolution-guided optimization of biosynthetic pathways. Proc. Natl Acad. Sci. USA 111, 17803–17808 (2014).

     Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

102. Matsumura, E. et al. Microbial production of novel sulphated alkaloids for drug discovery. Sci. Rep. 8, 7980 (2018).

     Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

103. Ro, D.-K. et al. Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440, 940–943 (2006).

     Article  ADS  CAS  PubMed  Google Scholar 

104. Rodriguez, A. et al. Engineering Escherichia coli to overproduce aromatic amino acids and derived compounds. Microb. Cell Fact. 13, 126 (2014).

     PubMed  PubMed Central  Google Scholar 

105. Qin, J. et al. Modular pathway rewiring of Saccharomyces cerevisiae enables high-narilevel production of L-ornithine. Nat. Commun. 6, 8224 (2015).

     Article  PubMed  Google Scholar 

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1. aExamples of engineered strains producing different compounds or compound classes that can be used as platform strains for the production of diverse downstream compounds. Yellow, core metabolite platform; blue, secondary metabolite platform