Comparative analysis of hapalindole, ambiguine and welwitindolinone gene clusters and reconstitution of indole-isonitrile biosynthesis from cyanobacteria

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• 作者：Melinda L Micallef (1)
  Deepti Sharma (2)
  Brittney M Bunn (2)
  Lena Gerwick (3)
  Rajesh Viswanathan (2)
  Michelle C Moffitt (1)
  
  1. School of Science and Health ; University of Western Sydney ; School of Science and Health ; Locked Bag 1797 ; 2751 ; Penrith ; NSW ; Australia
  2. Department of Chemistry ; Case Western Reserve University ; 2740 Millis Science Center ; Adelbert Road ; 44106 ; Cleveland ; OH ; USA
  3. Center for Marine Biotechnology and Biomedicine ; Scripps Institution of Oceanography ; University of California San Diego ; 92093 ; La Jolla ; CA ; USA
  
• 刊名：BMC Microbiology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,840 KB
• 参考文献：1. Richter, JM, Ishihara, Y, Masuda, T, Whitefield, BW, Llamas, T, Pohjakallio, A, Baran, PS (2008) Enantiospecific total synthesis of the hapalindoles, fischerindoles, and welwitindolinones via a redox economic approach. J Am Chem Soc 130: pp. 17938-17954 10.1021/ja806981k" target="_blank" title="It opens in new window">CrossRef
  2. Smith, CD, Zilfou, JT, Stratmann, K, Patterson, GM, Moore, RE (1995) Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance. Mol Pharmacol 47: pp. 241-247
  3. Zhang, X, Smith, CD (1996) Microtubule effects of welwistatin, a cyanobacterial indolinone that circumvents multiple drug resistance. Mol Pharmacol 49: pp. 288-294
  4. Mo, S, Krunic, A, Santarsiero, BD, Franzblau, SG, Orjala, J (2010) Hapalindole-related alkaloids from the cultured cyanobacterium Fischerella ambigua. Phytochemistry 71: pp. 2116-2123 10.1016/j.phytochem.2010.09.004" target="_blank" title="It opens in new window">CrossRef
  5. Mo, S, Krunic, A, Chlipala, G, Orjala, J (2009) Antimicrobial ambiguine isonitriles from the cyanobacterium Fischerella ambigua. J Nat Prod 72: pp. 894-899 10.1021/np800751j" target="_blank" title="It opens in new window">CrossRef
  6. Kim, H, Lantvit, D, Hwang, CH, Kroll, DJ, Swanson, SM, Franzblau, SG, Orjala, J (2012) Indole alkaloids from two cultured cyanobacteria, Westiellopsis sp and Fischerella muscicola. Bioorg Med Chem 20: pp. 5290-5295 10.1016/j.bmc.2012.06.030" target="_blank" title="It opens in new window">CrossRef
  7. Hillwig, ML, Zhu, Q, Liu, X (2013) Biosynthesis of ambiguine indole alkaloids in cyanobacterium Fischerella ambigua. ACS Chem Biol 9: pp. 372-377 10.1021/cb400681n" target="_blank" title="It opens in new window">CrossRef
  8. Hillwig, ML, Fuhrman, HA, Ittiamornkul, K, Sevco, TJ, Kwak, DH, Liu, X (2014) Identification and characterization of a welwitindolinone alkaloid biosynthetic gene cluster in the stigonematalean cyanobacterium Hapalosiphon welwitschii. Chem Bio Chem 15: pp. 665-669
  9. Becher, PG, Keller, S, Jung, G, S眉ssmuth, RD, J眉ttner, F (2007) Insecticidal activity of 12-epi-hapalindole J isonitrile. Phytochemistry 68: pp. 2493-2497 10.1016/j.phytochem.2007.06.024" target="_blank" title="It opens in new window">CrossRef
  10. Stratmann, K, Moore, RE, Bonjouklian, R, Deeter, JB, Patterson, GML, Shaffer, S, Smith, CD, Smitka, TA (1994) Welwitindolinones, unusual alkaloids from the blue-green algae Hapalosiphon welwitschii and Westiella intricata: relationship to fischerindoles and hapalinodoles. J Am Chem Soc 116: pp. 9935-9942 10.1021/ja00101a015" target="_blank" title="It opens in new window">CrossRef
  11. Rantala, A, Fewer, DP, Hisbergues, M, Rouhiainen, L, Vaitomaa, J, B枚rner, T, Sivonen, K (2004) Phylogenetic evidence for the early evolution of microcystin synthesis. Proc Natl Acad Sci U S A 101: pp. 568-573 10.1073/pnas.0304489101" target="_blank" title="It opens in new window">CrossRef
  12. Murray, SA, Mihali, TK, Neilan, BA (2011) Extraordinary conservation, gene loss, and positive selection in the evolution of an ancient neurotoxin. Mol Biol Evol 28: pp. 1173-1182 10.1093/molbev/msq295" target="_blank" title="It opens in new window">CrossRef
  13. D鈥橝gostino, PM, Moffitt, MC, Neilan, BA (2014) Current Knowledge of Paralytic Shellfish Toxin Biosynthesis, Molecular Detection and Evolution. Toxins and Biologically Active Compounds from Microalgae. CRC Press, Boca Raton, FL, pp. 251-280 10.1201/b16569-13" target="_blank" title="It opens in new window">CrossRef
  14. Huber, U, Moore, RE, Patterson, GML (1998) Isolation of a nitrile-containing indole alkaloid from the terrestrial blue-green alga Hapalosiphon delicatulus. J Nat Prod 61: pp. 1304-1306 10.1021/np9801561" target="_blank" title="It opens in new window">CrossRef
  15. Hall, GC, Flick, MB, Gherna, RL, Jensen, RA (1982) Biochemical diversity for biosynthesis of aromatic amino acids among the cyanobacteria. J Bacteriol 149: pp. 65-78
  16. Brady, SF, Clardy, J (2005) Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew Chem 117: pp. 7225-7227 10.1002/ange.200501941" target="_blank" title="It opens in new window">CrossRef
  17. Clarke-Pearson, MF, Brady, SF (2008) Paerucumarin, a new metabolite produced by the pvc gene cluster from Pseudomonas aeruginosa. J Bacteriol 190: pp. 6927 10.1128/JB.00801-08" target="_blank" title="It opens in new window">CrossRef
  18. McWilliam, H, Li, W, Uludag, M, Squizzato, S, Park, YM, Buso, N, Cowley, AP, Lopez, R (2013) Analysis tool web services from the EMBL-EBI. Nucleic Acids Res 41: pp. W597-W600 10.1093/nar/gkt376" target="_blank" title="It opens in new window">CrossRef
  19. Daum, M, Herrmann, S, Wilkinson, B, Bechthold, A (2009) Genes and enzymes involved in bacterial isoprenoid biosynthesis. Curr Opin Chem Biol 13: pp. 180-188 10.1016/j.cbpa.2009.02.029" target="_blank" title="It opens in new window">CrossRef
  20. Tello, M, Kuzuyama, T, Heide, L, Noel, J, Richard, S (2008) The ABBA family of aromatic prenyltransferases: broadening natural product diversity. Cell Mol Life Sci 65: pp. 1459-1463 10.1007/s00018-008-7579-3" target="_blank" title="It opens in new window">CrossRef
  21. Pojer, F, Wemakor, E, Kammerer, B, Chen, H, Walsh, CT, Li, S-M, Heide, L (2003) CloQ, a prenyltransferase involved in clorobiocin biosynthesis. Proc Natl Acad Sci U S A 100: pp. 2316-2321 10.1073/pnas.0337708100" target="_blank" title="It opens in new window">CrossRef
  22. Kling, E, Schmid, C, Unversucht, S, Wage, T, Zehner, S, Pee, KH Enzymatic Incorporation of Halogen Atoms into Natural Compounds. In: Wohlleben, W, Spellig, T, M眉ller-Tiemann, B eds. (2005) Biocombinatorial Approaches for Drug Finding. Springer, Berlin Heidelberg, pp. 165-194 10.1007/3-540-27055-8_8" target="_blank" title="It opens in new window">CrossRef
  23. Keller, S, Wage, T, Hohaus, K, H枚lzer, M, Eichhorn, E, P茅e, K-H (2000) Purification and partial characterization of tryptophan 7-halogenase (PrnA) from Pseudomonas fluorescens. Angew Chem Int Edit 39: pp. 2300-2302 10.1002/1521-3773(20000703)39:13<2300::AID-ANIE2300>3.0.CO;2-I" target="_blank" title="It opens in new window">CrossRef
  24. P茅e, K-H, Patallo, E (2006) Flavin-dependent halogenases involved in secondary metabolism in bacteria. Appl Microbiol Biotechnol 70: pp. 631-641 10.1007/s00253-005-0232-2" target="_blank" title="It opens in new window">CrossRef
  25. Rippka, R, Deruelles, J, Waterbury, JB, Herdman, M, Stanier, RY (1979) Generic assignments, strain histories and properties of pure cultures of cyanobacteria. J Gen Microbiol 111: pp. 1-61 10.1099/00221287-111-1-1" target="_blank" title="It opens in new window">CrossRef
  26. Morin, N, Vallaeys, T, Hendrickx, L, Natalie, L, Wilmotte, A (2010) An efficient DNA isolation protocol for filamentous cyanobacteria of the genus Arthrospira. J Microbiol Methods 80: pp. 148-154 10.1016/j.mimet.2009.11.012" target="_blank" title="It opens in new window">CrossRef
  27. Wilson, K (2001) Preparation of Genomic DNA from Bacteria. Current Protocols in Molecular Biology. John Wiley & Sons, Inc, New York
  28. Ausubel, F, Brent, R, Kingston, R, Moore, D, Seidman, J, Smith, J, Struhl, K (1996) Short Protocols in Molecular Biology. John Wiley & Sons, New York
  29. Mustafa, E (2011) Ambigols A-C and Tjipanazole D: Bioinformatic Analysis of their Putative Biosynthetic Gene Clusters. University of Bonn, Institute for Pharmaceutical Biology, Germany
  30. Altschul, SF, Gish, W, Miller, W, Myers, EW, Lipman, DJ (1990) Basic local alignment search tool. J Mol Biol 215: pp. 403-410 10.1016/S0022-2836(05)80360-2" target="_blank" title="It opens in new window">CrossRef
  31. Jukes, TH, Cantor, CR (1969) Evolution of Protein Molecules. Academic, New York
  32. Dorrestein, PC, Yeh, E, Garneau-Tsodikova, S, Kelleher, NL, Walsh, CT (2005) Dichlorination of a pyrrolyl-S-carrier protein by FADH2-dependent halogenase PltA during pyoluteorin biosynthesis. Proc Natl Acad Sci U S A 102: pp. 13843-13848 10.1073/pnas.0506964102" target="_blank" title="It opens in new window">CrossRef
  33. Hoppe, I, Sch枚llkopf, U (1984) Synthesis and biological activities of the antibiotic B 371 and its analogs. Liebigs Ann Chem 1984: pp. 600-607 10.1002/jlac.198419840317" target="_blank" title="It opens in new window">CrossRef
  34. Drake, EJ, Gulick, AM (2008) Three-dimensional structures of Pseudomonas aeruginosa PvcA and PvcB, two proteins involved in the synthesis of 2-isocyano-6,7-dihydroxycoumarin. J Mol Biol 384: pp. 193-205 10.1016/j.jmb.2008.09.027" target="_blank" title="It opens in new window">CrossRef
  
• 刊物主题：Microbiology; Biological Microscopy; Fungus Genetics; Parasitology; Virology; Life Sciences, general;
• 出版者：BioMed Central
• ISSN：1471-2180

文摘

Background The hapalindole-type family of natural products is a group of hybrid isoprenoid-indole alkaloids, produced solely by members of the Subsection V cyanobacterial strains. This family broadly includes the hapalindoles, welwitindolinones, fisherindoles and ambiguines amongst others, all of which have an isonitrile- or isothiocyanate-containing indole alkaloid skeleton, with a cyclized isoprene unit. The hapalindoles are diversified into the welwitindolinones, fischerindoles and ambiguines through the employment of tailoring oxygenase, methyltransferase and prenyltransferase enzymes. We compare the genetic basis for the biosynthesis of this diverse group of natural products and identify key early biosynthetic intermediates. Results Whole genome sequencing of freshwater and terrestrial cyanobacteria Westiella intricata UH strain HT-29-1, Hapalosiphon welwitschii UH strain IC-52-3, Fischerella ambigua UTEX 1903 and Fischerella sp. ATCC 43239 led to the identification of a candidate hapalindole-type gene cluster in each strain. These were compared with the recently published ambiguine and welwitindolinone gene clusters and four unpublished clusters identified within publicly available genomes. We present detailed comparative bioinformatic analysis of the gene clusters and the biosynthesis of a pivotal indole-isonitrile intermediate resulting in both cis and trans geometrical isomers. Enzyme analyses and metabolite extractions from two hapalindole-producing Fischerella strains indicate the presence of cis and trans indole-isonitriles as biosynthetic intermediates in the early steps of the pathway. Conclusions Interestingly, the organization of the welwitindolinone gene cluster is conserved in all producing strains but distinct from the hapalindole and ambiguine clusters. Enzymatic assays using WelI1 and WelI3 from Westiella intricata UH strain HT-29-1 demonstrated the ability to catalyze the formation of both cis and trans geometrical isomers when using a cell lysate. The enzymatic and metabolic characterization of both cis and trans indole-isonitrile intermediates implies conservation of their stereochemical integrity towards members of the ambiguine and welwitindolinone products. In summary, we present data that supports a unified biosynthetic pathway towards hapalindoles in nine individual species of cyanobacteria. Diversification of the pathway occurs later through the employment of specialized enzymatic steps towards fischerindoles, ambiguines and welwitindolinones.