Decoding and reprogramming complex polyketide assembly lines: Prospects for synthetic biology

Trends in Biochemical Sciences

Volumn 40, Issue 4, 2015, Pages 189-199

  Hertweck, Christian ^a,b  

^a HANS KNÖLL INSTITUTE   (Germany)

^b FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

Author keywords

Antibiotics; Biosynthesis; Macrolides; Modular polyketide synthase; Thiotemplate

Indexed keywords

MOLECULAR SCAFFOLD; POLYKETIDE; POLYKETIDE SYNTHASE; SCAFFOLD PROTEIN;

BACTERIAL GENOME; BIOCATALYST; BIOSYNTHESIS; CATALYSIS; CYCLIZATION; DATA MINING; DNA MODIFICATION; DNA RECOMBINATION; ENZYME ACTIVITY; ENZYME ANALYSIS; GENETIC CODE; GENETIC ENGINEERING; GENETIC VARIABILITY; GENOMICS; MOLECULAR RECOGNITION; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; REVIEW; STRUCTURE ANALYSIS; SYNTHETIC BIOLOGY; CHEMISTRY; METABOLISM; PROCEDURES;

BACTERIA (MICROORGANISMS);

POLYKETIDE SYNTHASES; POLYKETIDES; SYNTHETIC BIOLOGY;

EID: 84925340903     PISSN: 09680004     EISSN: 13624326     Source Type: Journal    
DOI: 10.1016/j.tibs.2015.02.001     Document Type: Review

References (81)

1. Hertweck C. The biosynthetic logic of polyketide diversity. Angew. Chem. Int. Ed. 2009, 48:4688-4716.
2. Dalby S.M., Paterson I. Synthesis of polyketide natural products and analogs as promising anticancer agents. Curr. Opin. Drug. Discov. Devel. 2010, 13:777-794.
3. Prusov E.V. Total synthesis of antibiotics: recent achievements, limitations, and perspectives. Appl. Microbiol. Biotechnol. 2013, 97:2773-2795.
4. Tibrewal N., Tang Y. Biocatalysts for natural product biosynthesis. Annu. Rev. Chem. Biomol. Eng. 2014, 5:347-366.
5. Meier J.L., Burkart M.D. The chemical biology of modular biosynthetic enzymes. Chem. Soc. Rev. 2009, 38:2012-2045.
6. Piel J. Biosynthesis of polyketides by trans-AT polyketide synthases. Nat. Prod. Rep. 2010, 27:996-1047.
7. Kwan D.H., Schulz F. The stereochemistry of complex polyketide biosynthesis by modular polyketide synthases. Molecules 2011, 16:6092-6115.
8. Kopp M., Marahiel M.A. Macrocyclization strategies in polyketide and nonribosomal peptide biosynthesis. Nat. Prod. Rep. 2007, 24:735-749.
9. Olano C., et al. Post-PKS tailoring steps in natural product-producing actinomycetes from the perspective of combinatorial biosynthesis. Nat. Prod. Rep. 2010, 27:571-616.
10. Fischbach M.A., Walsh C.T. Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem. Rev. 2006, 106:3468-3496.
11. Weissman K.J., Leadlay P.F. Combinatorial biosynthesis of reduced polyketides. Nat. Rev. Microbiol. 2005, 3:925-936.
12. Wong F.T., Khosla C. Combinatorial biosynthesis of polyketides - a perspective. Curr. Opin. Chem. Biol. 2012, 16:117-123.
13. Poust S., et al. Narrowing the gap between the promise and reality of polyketide synthases as a synthetic biology platform. Curr. Opin. Biotechnol. 2014, 30C:32-39.
14. Khosla C., et al. Assembly line polyketide synthases: mechanistic insights and unsolved problems. Biochemistry 2014, 53:2875-2883.
15. Keatinge-Clay A.T. The structures of type I polyketide synthases. Nat. Prod. Rep. 2012, 29:1050-1073.
16. Dutta S., et al. Structure of a modular polyketide synthase. Nature 2014, 510:512-517.
17. Whicher J.R., et al. Structural rearrangements of a polyketide synthase module during its catalytic cycle. Nature 2014, 510:560-564.
18. Kapur S., et al. Reprogramming a module of the 6-deoxyerythronolide B synthase for iterative chain elongation. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:4110-4115.
19. Busch B., et al. Interchenar retrotransfer of aureothin intermediates in an iterative polyketide synthase module. J. Am. Chem. Soc. 2012, 134:12382-12385.
20. Busch B., et al. Multifactorial control of iteration events in a modular polyketide assembly line. Angew. Chem. Int. Ed. 2013, 52:5285-5289.
21. Nguyen T., et al. Exploiting the mosaic structure of trans-acyl transferase polyketide synthases for natural product discovery and pathway dissection. Nat. Biotechnol. 2008, 26:225-233.
22. Jenner M., et al. Substrate specificity in ketosynthase domains from trans-AT polyketide synthases. Angew. Chem. Int. Ed. 2012, 52:1143-1147.
23. Jensen K., et al. Polyketide proofreading by an acyltransferase-like enzyme. Chem. Biol. 2012, 19:329-339.
24. Musiol E.M., et al. Supramolecular templating in kirromycin biosynthesis: the acyltransferase KirCII loads ethylmalonyl-CoA extender onto a specific ACP of the trans-AT PKS. Chem. Biol. 2011, 18:438-444.
25. Helfrich E.J., et al. Recent advances in genome-based polyketide discovery. Curr. Opin. Biotechnol. 2014, 29:107-115.
26. Winter J.M., et al. Genomics-inspired discovery of natural products. Curr. Opin. Chem. Biol. 2011, 15:22-31.
27. Herrmann S., et al. Site-specific recombination strategies for engineering actinomycete genomes. Appl. Environ. Microbiol. 2012, 78:1804-1812.
28. Cummings M., et al. Steps towards the synthetic biology of polyketide biosynthesis. FEMS Microbiol. Lett. 2014, 351:116-125.
29. Ongley S.E., et al. Recent advances in the heterologous expression of microbial natural product biosynthetic pathways. Nat. Prod. Rep. 2013, 30:1121-1138.
30. Yuzawa S., et al. Heterologous production of polyketides by modular type I polyketide synthases in Escherichia coli. Curr. Opin. Biotechnol. 2012, 23:727-735.
31. Oßwald C., et al. Modular construction of a functional artificial epothilone polyketide pathway. ACS Synth. Biol. 2014, 3:759-772.
32. Kushnir S., et al. Minimally invasive mutagenesis gives rise to a biosynthetic polyketide library. Angew. Chem. Int. Ed. 2012, 51:10664-10669.
33. Sugimoto Y., et al. Rational design of modular polyketide synthases: morphing the aureothin pathway into a luteoreticulin assembly line. Angew. Chem. Int. Ed. 2014, 53:1560-1564.
34. Sugimoto Y., et al. Freedom and constraint in engineered noncolinear polyketide assembly lines. Chem. Biol. 2015, 22:229-240.
35. Moore B.S., Hertweck C. Biosynthesis and attachment of novel bacterial polyketide synthase starter units. Nat. Prod. Rep. 2002, 19:70-99.
36. Kirschning A., Hahn F. Merging chemical synthesis and biosynthesis: a new chapter in the total synthesis of natural products and natural product libraries. Angew. Chem. Int. Ed. 2012, 51:4012-4022.
37. Chan Y.A., et al. Biosynthesis of polyketide synthase extender units. Nat. Prod. Rep. 2009, 26:90-114.
38. Wilson M.C., Moore B.S. Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity. Nat. Prod. Rep. 2012, 29:72-86.
39. Quade N., et al. Unusual carbon fixation gives rise to diverse polyketide extender units. Nat. Chem. Biol. 2012, 8:117-124.
40. Mo S., et al. Biosynthesis of the allylmalonyl-CoA extender unit for the FK506 polyketide synthase proceeds through a dedicated polyketide synthase and facilitates the mutasynthesis of analogues. J. Am. Chem. Soc. 2011, 133:976-985.
41. Xu Z., et al. A branched extender unit shared between two orthogonal polyketide pathways in an endophyte. Angew. Chem. Int. Ed. 2011, 50:4667-4670.
42. Hughes A.J., Keatinge-Clay A. Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and functional showcasing of Streptomyces coelicolor MatB. Chem. Biol. 2011, 18:165-176.
43. Koryakina I., et al. Promiscuity of a modular polyketide synthase towards natural and non-natural extender units. Org. Biomol. Chem. 2013, 11:4449-4458.
44. Dunn B.J., Khosla C. Engineering the acyltransferase substrate specificity of assembly line polyketide synthases. J. R. Soc. Interface 2013, 10:20130297.
45. Koryakina I., Williams G.J. Mutant malonyl-CoA synthetases with altered specificity for polyketide synthase extender unit generation. ChemBioChem 2011, 12:2289-2293.
46. Bravo-Rodriguez K., et al. Predicted incorporation of non-native substrates by a polyketide synthase yields bioactive natural product derivatives. ChemBioChem 2014, 15:1991-1997.
47. Sundermann U., et al. Enzyme-directed mutasynthesis: a combined experimental and theoretical approach to substrate recognition of a polyketide synthase. ACS Chem. Biol. 2013, 8:443-450.
48. Walker M.C., et al. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways. Science 2013, 341:1089-1094.
49. Haines A.S., et al. A conserved motif flags acyl carrier proteins for beta-branching in polyketide synthesis. Nat. Chem. Biol. 2013, 9:685-692.
50. Kusebauch B., et al. Polyketide-chain branching by an enzymatic Michael addition. Angew. Chem. Int. Ed. 2009, 48:5001-5004.
51. Bretschneider T., et al. Vinylogous chain branching catalysed by a dedicated polyketide synthase module. Nature 2013, 502:124-128.
52. Yin M., et al. Cycloheximide and actiphenol production in Streptomyces sp. YIM56141 governed by single biosynthetic machinery featuring an acyltransferase-less type I polyketide synthase. Org. Lett. 2014, 16:3072-3075.
53. Heine D., et al. Enzymatic polyketide chain branching to give substituted lactone, lactam, and glutarimide heterocycles. Angew. Chem. Int. Ed. 2014, 53:11645-11649.
54. Hari T.P., et al. An evolutionary model encompassing substrate specificity and reactivity of type I polyketide synthase thioesterases. ChemBioChem 2014, 15:2656-2661.
55. He H.Y., et al. Quartromicin biosynthesis: two alternative polyketide chains produced by one polyketide synthase assembly line. Chem. Biol. 2012, 19:1313-1323.
56. Hashimoto T., et al. Biosynthesis of versipelostatin: identification of an enzyme-catalyzed [4+2]-cycloaddition required for macrocyclization of spirotetronate-containing polyketides. J. Am. Chem. Soc. 2015, 137:572-575.
57. Lou L., et al. Biosynthesis of HSAF, a tetramic acid-containing macrolactam from Lysobacter enzymogenes. J. Am. Chem. Soc. 2011, 133:643-645.
58. Luo Y., et al. Activation and characterization of a cryptic polycyclic tetramate macrolactam biosynthetic gene cluster. Nat. Commun. 2013, 4:2894.
59. Li Y., et al. Iterative assembly of two separate polyketide chains by the same single-module bacterial polyketide synthase in the biosynthesis of HSAF. Angew. Chem. Int. Ed. 2014, 53:7524-7530.
60. Zhang G., et al. Mechanistic insights into polycycle formation by reductive cyclization in ikarugamycin biosynthesis. Angew. Chem. Int. Ed. 2014, 53:4840-4844.
61. Antosch J., et al. Heterologous reconstitution of ikarugamycin biosynthesis in E. coli. Angew. Chem. Int. Ed. 2014, 53:3011-3014.
62. Nakamura H., et al. Cylindrocyclophane biosynthesis involves functionalization of an unactivated carbon center. J. Am. Chem. Soc. 2012, 134:18518-18521.
63. Fuchs S.W., et al. Formation of 1,3-cyclohexanediones and resorcinols catalyzed by a widely occuring ketosynthase. Angew. Chem. Int. Ed. 2013, 52:4108-4112.
64. Erol O., et al. Biosynthesis of the myxobacterial antibiotic corallopyronin A. ChemBioChem 2010, 11:1253-1265.
65. Sucipto H., et al. Exploring chemical diversity of g-pyrone antibiotics: molecular basis of myxopyronin biosynthesis. ChemBioChem 2013, 14:1581-1589.
66. Franke J., et al. Genomics-driven discovery of burkholderic acid, a noncanonical, cryptic polyketide from human pathogenic Burkholderia species. Angew. Chem. Int. Ed. 2012, 51:11611-11615.
67. Biggins J.B., et al. Malleilactone, a polyketide synthase-derived virulence factor encoded by the cryptic secondary metabolome of Burkholderia pseudomallei group pathogens. J. Am. Chem. Soc. 2012, 134:13192-13195.
68. Gallimore A.R. The biosynthesis of polyketide-derived polycyclic ethers. Nat. Prod. Rep. 2009, 26:266-280.
69. Smith L., et al. Analysis of specific mutants in the lasalocid gene cluster: evidence for enzymatic catalysis of a disfavoured polyether ring closure. ChemBioChem 2008, 9:2967-2975.
70. Hotta K., et al. Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis. Nature 2012, 483:355-358.
71. Zocher G., et al. Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 2011, 133:2292-2302.
72. Henrot M., et al. Convergent asymmetric synthesis of (+)-aureothin employing an oxygenase-mediated resolution step. Angew. Chem. Int. Ed. 2012, 51:9587-9591.
73. Pöplau P., et al. An enzymatic domain for the formation of cyclic ethers in complex polyketides. Angew. Chem. Int. Ed. 2013, 52:13215-13218.
74. Berkhan G., Hahn F. A dehydratase domain in ambruticin biosynthesis displays additional activity as a pyran-forming cyclase. Angew. Chem. Int. Ed. 2014, 53:14240-14244.
75. Takahashi S., et al. Reveromycin A biosynthesis uses RevG and RevJ for stereospecific spiroacetal formation. Nat. Chem. Biol. 2011, 7:461-468.
76. Sun P., et al. Spiroketal formation and modification in avermectin biosynthesis involves a dual activity of AveC. J. Am. Chem. Soc. 2013, 135:1540-1548.
77. Hiratsuka T., et al. Biosynthesis of the structurally unique polycyclopropanated polyketide-nucleoside hybrid jawsamycin (FR-900848). Angew. Chem. Int. Ed. 2014, 53:5423-5426.
78. Teta R., et al. Genome mining reveals trans-AT polyketide synthase directed antibiotic biosynthesis in the bacterial phylum bacteroidetes. ChemBioChem 2010, 18:2506-2512.
79. Dehn R., et al. Molecular basis of elansolid biosynthesis: evidence for an unprecedented quinone methide initiated intramolecular Diels-Alder cycloaddition/macrolactonization. Angew. Chem. Int. Ed. 2011, 50:3882-3887.
80. Ding L., et al. Divergolides A-D from a mangrove endophyte reveal an unparalleled plasticity in ansa-macrolide biosynthesis. Angew. Chem. Int. Ed. 2011, 50:1630-1634.
81. Xu Z., et al. Biosynthetic code for divergolide assembly in a bacterial mangrove endophyte. ChemBioChem 2014, 15:1274-1279.