Strategies for terpenoid overproduction and new terpenoid discovery

Current Opinion in Biotechnology

Volumn 48, Issue , 2017, Pages 234-241

  Bian, Guangkai ^a   Deng, Zixin ^a,b   Liu, Tiangang ^a,b  

^a WUHAN UNIVERSITY   (China)

^b Centre for Biomedicine Research   (China)

Author keywords

[No Author keywords available]

Indexed keywords

METABOLIC ENGINEERING;

CYCLASES; IN-VITRO; MICROBIAL SYSTEM; NATURAL PRODUCTS; PATHWAY ENGINEERINGS; PRECURSOR SUPPLY; SYSTEMATIC ENGINEERING; TERPENOIDS;

LIPIDS;

ACETYL COENZYME A; ADENYLATE CYCLASE; ASPERTERPENDIENE; ASPERTERPENOL A; ASPERTERPENOL B; ASTAXANTHIN; CYTOCHROME; DIMETHYLALLYL DIPHOSPHATE; DIMETHYLALLYLTRANSFERASE; DITERPENE; FARNESYL DIPHOSPHATE; GERANYLGERANYL PYROPHOSPHATE; HEMITERPENE; ISOPENTENYL DIPHOSPHATE; ISOPENTENYL DIPHOSPHATE DELTA ISOMERASE; LYCOPENE; MANGICDIENE; MANGICOL A; MANGICOL B; PYROPHOSPHATE; SESQUITERPENE; SESTERTERPENE; TERPENE DERIVATIVE; TERPENOID; TRITERPENE; UNCLASSIFIED DRUG; TERPENE;

BIOCHEMISTRY; BIOSYNTHESIS; CHEMICAL STRUCTURE; ENZYME ACTIVITY; ESCHERICHIA COLI; GENOME ANALYSIS; HOST; METABOLIC ENGINEERING; METABOLOMICS; MICROBIAL ACTIVITY; NONHUMAN; PRECURSOR; PRIORITY JOURNAL; PROTEOMICS; REVIEW; SACCHAROMYCES CEREVISIAE; WHOLE CELL; CELLS; CHEMISTRY; GENOME; METABOLISM; PROCEDURES;

BIOSYNTHETIC PATHWAYS; CELLS; GENOME; METABOLIC ENGINEERING; TERPENES;

EID: 85026636276     PISSN: 09581669     EISSN: 18790429     Source Type: Journal    
DOI: 10.1016/j.copbio.2017.07.002     Document Type: Review

References (53)

1. Paddon, C.J., Westfall, P., Pitera, D., Benjamin, K., Fisher, K., McPhee, D., Leavell, M., Tai, A., Main, A., Eng, D., High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496 (2013), 528–532.
2. Ajikumar, P.K., Xiao, W.H., Tyo, K.E.J., Wang, Y., Simeon, F., Leonard, E., Mucha, O., Phon, T.H., Pfeifer, B., Stephanopoulos, G., Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330 (2010), 70–74.
3. Lv, X., Wang, F., Zhou, P., Ye, L., Xie, W., Xu, H., Yu, H., Dual regulation of cytoplasmic and mitochondrial acetyl-CoA utilization for improved isoprene production in Saccharomyces cerevisiae. Nat Commun, 7, 2016, 12851 Dual engineering of acetyl-CoA utilization in the cytoplasm and mitochondria results in synergistic effects on isoprene production in S. cerevisiae. Coupled with the two-phase culture process and aerobic fed-batch fermentation, the highest titer of isoprene was achieved in engineered eukaryotes.
4. Pemberton, T.A., Chen, M., Harris, G.G., Chou, W.K., Duan, L., Köksal, M., Genshaft, A.S., Cane, D.E., Christianson, D.W., Exploring the influence of domain architecture on the catalytic function of diterpene synthases. Biochemistry 56 (2017), 2010–2023.
5. Croteau, R., Ketchum, R.E., Long, R.M., Kaspera, R., Wildung, M.R., Taxol biosynthesis and molecular genetics. Phytochem Rev 5 (2006), 75–97.
6. Xie, W., Lv, X., Ye, L., Zhou, P., Yu, H., Construction of lycopene-overproducing Saccharomyces cerevisiae by combining directed evolution and metabolic engineering. Metab Eng 30 (2015), 69–78 An unimpeded pathway was set up after increasing the supply of farnesyl diphosphate and strengthening the lycopene-forming pathway. Together with the overexpression of engineered CrtYB11M and the optimization of the two-stage feeding process of fed-batch fermentation, the yield of lycopene was increased to 1.61 g/L with a low yield of the byproduct squalene.
7. Kumaran AP, Lim CG, Li L, Ghosh S, Pirie C, Qualley A: Methods for production of oxygenated terpenes. Google Patents; 2016.
8. Lowry, B., Walsh, C.T., Khosla, C., In vitro reconstitution of metabolic pathways: insights into nature's chemical logic. Synlett 26 (2015), 1008–1025.
9. Zhu, F., Zhong, X., Hu, M., Lu, L., Deng, Z., Liu, T., In vitro reconstitution of mevalonate pathway and targeted engineering of farnesene overproduction in Escherichia coli. Biotechnol Bioeng 111 (2014), 1396–1405 From the in vitro reconstituted MVA pathway, the authors obtained an optimal ratio of synthetic components. A farnesene-overproducing E. coli strain was designed according to this information and resulted in high productivity and titer.
10. Korman, T.P., Opgenorth, P.H., Bowie, J.U., A synthetic biochemistry platform for cell free production of monoterpenes from glucose. Nat Commun, 8, 2017, 15526 Using glucose as a substrate, a biosynthetic pathway for monoterpene production was in vitro reconstituted. Twenty-seven enzymes and the supplies of ATP and NAD(P)H were optimized within this system. Unrestricted by cellular toxicity, high titers of limonene, pinene, and sabinene were produced at approximately the theoretical maximum yields.
11. Gao, S., Tong, Y., Zhu, L., Ge, M., Zhang, Y., Chen, D., Jiang, Y., Yang, S., Iterative integration of multiple-copy pathway genes in Yarrowia lipolytica for heterologous β-carotene production. Metab Eng 41 (2017), 192–201.
12. Zhu, F., Lu, L., Fu, S., Zhong, X., Hu, M., Deng, Z., Liu, T., Targeted engineering and scale up of lycopene overproduction in Escherichia coli. Process Biochem 50 (2015), 341–346.
13. Ma, T., Zhou, Y., Li, X., Zhu, F., Cheng, Y., Liu, Y., Deng, Z., Liu, T., Genome mining of astaxanthin biosynthetic genes from Sphingomonas sp. ATCC 55669 for heterologous overproduction in Escherichia coli. Biotechnol J 11 (2016), 228–237.
14. Bian, G., Yuan, Y., Tao, H., Shi, X., Zhong, X., Han, Y., Fu, S., Fang, C., Deng, Z., Liu, T., Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6. Biotechnol J, 2017.
15. Liu, Z., Zhang, Y., Jia, X., Hu, M., Deng, Z., Xu, Y., Liu, T., In vitro reconstitution and optimization of the entire pathway to convert glucose into fatty acid. ACS Synth Biol 6 (2017), 701–709.
16. Meadows, A.L., Hawkins, K.M., Tsegaye, Y., Antipov, E., Kim, Y., Raetz, L., Dahl, R.H., Tai, A., Mahatdejkul-Meadows, T., Xu, L., Rewriting yeast central carbon metabolism for industrial isoprenoid production. Nature 537 (2016), 694–697 The authors constructed a genome-scale model of S. cerevisiae to calculate the maximum theoretical yields and corresponding flux distributions and then systematically engineered the central carbon metabolism to balance energy and carbon flux, resulting in commercially efficient production of farnesene.
17. Zhao, J., Li, Q., Sun, T., Zhu, X., Xu, H., Tang, J., Zhang, X., Ma, Y., Engineering central metabolic modules of Escherichia coli for improving beta-carotene production. Metab Eng 17 (2013), 42–50.
18. Liu, H., Wang, Y., Tang, Q., Kong, W., Chung, W.-J., Lu, T., MEP pathway-mediated isopentenol production in metabolically engineered Escherichia coli. Microb Cell Fact, 13, 2014, 135.
19. Tippmann, S., Scalcinati, G., Siewers, V., Nielsen, J., Production of farnesene and santalene by Saccharomyces cerevisiae using fed-batch cultivations with RQ-controlled feed. Biotechnol Bioeng 113 (2016), 72–81.
20. Xie, W., Ye, L., Lv, X., Xu, H., Yu, H., Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae. Metab Eng 28 (2015), 8–18 A sequential control strategy regulated by glucose concentration was used to balance flux to the ergosterol and carotenoid pathways at the FPP branch point.
21. Zhang, F., Carothers, J.M., Keasling, J.D., Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids. Nat Biotechnol 30 (2012), 354–359.
22. Dahl, R.H., Zhang, F., Alonso-Gutierrez, J., Baidoo, E., Batth, T.S., Redding-Johanson, A.M., Petzold, C.J., Mukhopadhyay, A., Lee, T.S., Adams, P.D., Engineering dynamic pathway regulation using stress-response promoters. Nat Biotechnol 31 (2013), 1039–1046 Stress-response promoters were identified and successfully used in regulating farnesyl pyrophosphate production. Finally, in the absence of expensive inducers, the production of amorphadiene in E. coli was increased twofold to 1.6 g/L with low acetate accumulation and high cell growth rate.
23. Zhang, C., Chen, X., Stephanopoulos, G., Too, H.P., Efflux transporter engineering markedly improves amorphadiene production in Escherichia coli. Biotechnol Bioeng 113 (2016), 1755–1763.
24. Chen, Y., Xiao, W., Wang, Y., Liu, H., Li, X., Yuan, Y., Lycopene overproduction in Saccharomyces cerevisiae through combining pathway engineering with host engineering. Microb Cell Fact, 15, 2016, 113.
25. Katz, L., Baltz, R.H., Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43 (2016), 155–176.
26. He, Y., Hu, Z., Sun, W., Li, Q., Li, X.-N., Zhu, H., Huang, J., Liu, J., Wang, J., Xue, Y., Spiroaspertrione A, a bridged spirocyclic meroterpenoid, as a potent potentiator of oxacillin against methicillin-resistant Staphylococcus aureus from Aspergillus sp. TJ23. J Org Chem 82 (2017), 3125–3131.
27. Meguro, A., Tomita, T., Nishiyama, M., Kuzuyama, T., Identification and characterization of bacterial diterpene cyclases that synthesize the cembrane skeleton. ChemBioChem 14 (2013), 316–321.
28. Görner, C., Schrepfer, P., Redai, V., Wallrapp, F., Loll, B., Eisenreich, W., Haslbeck, M., Brück, T., Identification, characterization and molecular adaptation of class I redox systems for the production of hydroxylated diterpenoids. Microb Cell Fact, 15, 2016, 86.
29. Khaldi, N., Seifuddin, F.T., Turner, G., Haft, D., Nierman, W.C., Wolfe, K.H., Fedorova, N.D., SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 47 (2010), 736–741.
30. Weber, T., Blin, K., Duddela, S., Krug, D., Kim, H.U., Bruccoleri, R., Lee, S.Y., Fischbach, M.A., Müller, R., Wohlleben, W., antiSMASH 3.0 — a comprehensive resource for the genome mining of biosynthetic gene clusters. Nucleic Acids Res 43 (2015), W237–W243.
31. Yamada, Y., Kuzuyama, T., Komatsu, M., Shin-ya, K., Omura, S., Cane, D.E., Ikeda, H., Terpene synthases are widely distributed in bacteria. Proc Natl Acad Sci U S A 112 (2015), 857–862.
32. Bian, G., Han, Y., Hou, A., Yuan, Y., Liu, X., Deng, Z., Liu, T., Releasing the potential power of terpene synthases by a robust precursor supply platform. Metab Eng 42 (2017), 1–8 Under the combinatorial biosynthesis strategy, the potential of the promiscuous terpene cyclases FgMS and FgGS were fully displayed. Two new sesterterpenes and five new diterpenes with three new carbon skeletons were structurally characterized from the 12 identified products. Then, rational site-directed mutagenesis was carried out to further enhance product diversity. Six potentially new sesterterpenes were produced by F65L and F159G, and one was confirmed as a new sesterterpene.
33. Matsuda, Y., Mitsuhashi, T., Quan, Z., Abe, I., Molecular basis for stellatic acid biosynthesis: a genome mining approach for discovery of sesterterpene synthases. Org Lett 17 (2015), 4644–4647.
34. Qin, B., Matsuda, Y., Mori, T., Okada, M., Quan, Z., Mitsuhashi, T., Wakimoto, T., Abe, I., An unusual chimeric diterpene synthase from Emericella variecolor and its functional conversion into a sesterterpene synthase by domain swapping. Angew Chem Int Ed 54 (2015), 1–5.
35. Ye, Y., Minami, A., Mandi, A., Liu, C., Taniguchi, T., Kuzuyama, T., Monde, K., Gomi, K., Oikawa, H., Genome mining for sesterterpenes using bifunctional terpene synthases reveals a unified intermediate of di/sesterterpenes. J Am Chem Soc 137 (2015), 11846–11853 Using a genome mining approach, the bifunctional terpene synthase NfSS was characterized and coupled with cytochrome P450 monooxygenase (NfP450) to produce sesterterpenoids with new skeletons. The cyclization mechanisms were proposed by feeding with isotopically labeled precursors. The initial cyclization mechanisms of diterpene and sesterterpene were classified, and the unified biosynthetic pathway for sesterterpenes in group A was proposed.
36. Nielsen, J.C., Grijseels, S., Prigent, S., Ji, B., Dainat, J., Nielsen, K.F., Frisvad, J.C., Workman, M., Nielsen, J., Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species. Nat Microbiol, 2, 2017, 17044.
37. Li, Y.F., Tsai, K.J., Harvey, C.J., Li, J.J., Ary, B.E., Berlew, E.E., Boehman, B.L., Findley, D.M., Friant, A.G., Gardner, C.A., Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. Fungal Genet Biol 89 (2016), 18–28.
38. Zerbe, P., Hamberger, B., Yuen, M.M., Chiang, A., Sandhu, H.K., Madilao, L.L., Nguyen, A., Hamberger, B., Bach, S.S., Bohlmann, J., Gene discovery of modular diterpene metabolism in nonmodel systems. Plant Physiol 162 (2013), 1073–1091.
39. Andersen-Ranberg, J., Kongstad, K.T., Nielsen, M.T., Jensen, N.B., Pateraki, I., Bach, S.S., Hamberger, B., Zerbe, P., Staerk, D., Bohlmann, J., Expanding the landscape of diterpene structural diversity through stereochemically controlled combinatorial biosynthesis. Angew Chem Int Ed 55 (2016), 2142–2146.
40. Jia, M., Potter, K.C., Peters, R.J., Extreme promiscuity of a bacterial and a plant diterpene synthase enables combinatorial biosynthesis. Metab Eng 37 (2016), 24–34.
41. Zhuang, X., Chappell, J., Building terpene production platforms in yeast. Biotechnol Bioeng 112 (2015), 1854–1864.
42. Liu, Q., Xiao, L., Zhou, Y., Deng, K., Tan, G., Han, Y., Liu, X., Deng, Z., Liu, T., Development of Streptomyces sp. FR-008 as an emerging chassis. Synth Syst Biotechnol 1 (2016), 207–214.
43. Castillo, D.A., Kolesnikova, M.D., Matsuda, S.P., An effective strategy for exploring unknown metabolic pathways by genome mining. J Am Chem Soc 135 (2013), 5885–5894.
44. Matsuda, Y., Mitsuhashi, T., Lee, S., Hoshino, M., Mori, T., Okada, M., Zhang, H., Hayashi, F., Fujita, M., Abe, I., Astellifadiene: structure determination by NMR spectroscopy and crystalline sponge method, and elucidation of its biosynthesis. Angew Chem Int Ed 128 (2016), 5879–5882.
45. Jakociunas, T., Bonde, I., Herrgard, M., Harrison, S.J., Kristensen, M., Pedersen, L.E., Jensen, M.K., Keasling, J.D., Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae. Metab Eng 28 (2015), 213–222.
46. Li, Y., Lin, Z., Huang, C., Zhang, Y., Wang, Z., Tang, Y.J., Chen, T., Zhao, X., Metabolic engineering of Escherichia coli using CRISPR-Cas9 meditated genome editing. Metab Eng 31 (2015), 13–21.
47. Kim, S.K., Han, G.H., Seong, W., Kim, H., Kim, S.-W., Lee, D.-H., Lee, S.-G., CRISPR interference-guided balancing of a biosynthetic mevalonate pathway increases terpenoid production. Metab Eng 38 (2016), 228–240.
48. Michener, J.K., Smolke, C.D., High-throughput enzyme evolution in Saccharomyces cerevisiae using a synthetic RNA switch. Metab Eng 14 (2012), 306–316.
49. Mafu, S., Jia, M., Zi, J., Morrone, D., Wu, Y., Xu, M., Hillwig, M.L., Peters, R.J., Probing the promiscuity of ent-kaurene oxidases via combinatorial biosynthesis. Proc Natl Acad Sci U S A 113 (2016), 2526–2531 Based on the combinatorial biosynthetic approach, the promiscuous nature of the ent-kaurene oxidase AtKO was fully displayed by screening 22 labdane-related diterpenoid substrates in engineered E. coli, resulting in a large number of AtKO alcohols and acids.
50. Ignea, C., Ioannou, E., Georgantea, P., Loupassaki, S., Trikka, F.A., Kanellis, A.K., Makris, A.M., Roussis, V., Kampranis, S.C., Reconstructing the chemical diversity of labdane-type diterpene biosynthesis in yeast. Metab Eng 28 (2015), 91–103.
51. Zhuang, Y., Yang, G., Chen, X., Liu, Q., Zhang, X., Deng, Z., Feng, Y., Biosynthesis of plant-derived ginsenoside Rh2 in yeast via repurposing a key promiscuous microbial enzyme. Metab Eng 42 (2017), 25–32.
52. Furubayashi, M., Ikezumi, M., Takaichi, S., Maoka, T., Hemmi, H., Ogawa, T., Saito, K., Tobias, A.V., Umeno, D., A highly selective biosynthetic pathway to non-natural C50 carotenoids assembled from moderately selective enzymes. Nat Commun, 6, 2015, 7534.
53. Kolev, J.N., Zaengle, J.M., Ravikumar, R., Fasan, R., Enhancing the efficiency and regioselectivity of P450 oxidation catalysts by unnatural amino acid mutagenesis. ChemBioChem 15 (2014), 1001–1010.