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Bioactive molecules from Nocardia: diversity, bioactivities and biosynthesis

  • Dipesh Dhakal
  • Vijay Rayamajhi
  • Ravindra Mishra
  • Jae Kyung SohngEmail author
Metabolic Engineering and Synthetic Biology - Original Paper
  • 232 Downloads

Abstract

Nocardia spp. are catalase positive, aerobic, and non-motile Gram-positive filamentous bacteria. Many Nocarida spp. have been reported as unusual causes of diverse clinical diseases in both humans and animals. Therefore, they have been studied for a long time, primarily focusing on strain characterization, taxonomic classification of new isolates, and host pathophysiology. Currently, there are emerging interests in isolating bioactive molecules from diverse actinobacteria including Nocardia spp. and studying their biosynthetic mechanisms. In addition, these species possess significant metabolic capacity, which has been utilized for generating diverse functionalized bioactive molecules by whole cell biotransformation. This review summarizes the structural diversity and biological activities of compounds biosynthesized or biotransformed by Nocardia spp. Furthermore, the recent advances on biosynthetic mechanisms and genetic engineering approaches for enhanced production or structural/functional modification are presented.

Keywords

Nocardia spp. Bioactive compounds Biosynthetic mechanism Structural modifications Biotransformation 

Notes

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2014R1A2A2A01002875, JKS) and (NRF-2017R1D1A1B03036273, DD). The authors want to dedicate this manuscript in honor of Professors Heinz Floss and Chris Walsh for inspiring research in the field of natural products.

Supplementary material

10295_2018_2120_MOESM1_ESM.docx (316 kb)
Supplementary material 1 (DOCX 317 kb)

References

  1. 1.
    Anada M, Hanari T, Kakita K, Kurosaki Y, Katsuse K, Sunadoi Y, Jinushi Y, Takeda K, Matsunaga S, Hashimoto S (2017) Total Synthesis of Brasilicardins A and C. Org Lett 19:5581–5584.  https://doi.org/10.1021/acs.orglett.7b02728 Google Scholar
  2. 2.
    Aoki H, Sakai H, Kohsaka M, Konomi T, Hosoda J, Kubochi Y, Iguchi E, Imanaks H (1976) Nocardicin A, a new monocyclic β-lactam antibiotic. I. Discovery, isolation and characterization. J Antibiot 29:492–500Google Scholar
  3. 3.
    Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J, Cotter PD (2013) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30:108–160.  https://doi.org/10.1039/c2np20085f Google Scholar
  4. 4.
    Ayeleso TB, Matumba MG, Mukwevho E (2017) Oleanolic acid and its derivatives: biological activities and therapeutic potential in chronic diseases. Molecules 22:1915.  https://doi.org/10.3390/molecules22111915 Google Scholar
  5. 5.
    Baltz RH (2010) Streptomyces and Saccharopolyspora hosts for heterologous expression of secondary metabolite gene clusters. J Ind Microbiol Biotechnol 37:759–772Google Scholar
  6. 6.
    Bérdy J (2005) Bioactive microbial metabolites. J Antibiot 58:1–26Google Scholar
  7. 7.
    Brown GM, Dubreuil P, Ichhaporia FM, Desnoyers JE (1970) Synthesis and properties of some α-D-alkyl glucosides and mannosides: apparent molal volumes and solubilization of nitrobenzene in water at 25 °C. Can J Chem 48:2525–2531Google Scholar
  8. 8.
    Brown-Elliott BA, Brown JM, Conville PS, Wallace RJ (2006) Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy. Clin Microbiol Rev 19:259–282Google Scholar
  9. 9.
    Buckland BC, Dunnill P, Lilly MD (1975) The enzymatic transformation of water-insoluble reactants in nonaqueous solvents. Conversion of cholesterol to cholest-4-ene-3-one by a Nocardia sp. Biotechnol Bioeng 17:815–826Google Scholar
  10. 10.
    Cane DE, Yang CC (1984) Biosynthetic origin of the carbon skeleton and oxygen atoms of nargenicin A1. J Am Chem Soc 106:784–787.  https://doi.org/10.1021/ja00315a052 Google Scholar
  11. 11.
    Cane DE, Tan W, Ott WR (1993) Nargenicin biosynthesis. Incorporation of polyketide chain elongation intermediates and support for a proposed intramolecular Diels-Alder cyclization. J Am Chem Soc 115:527–535.  https://doi.org/10.1021/ja00055a024 Google Scholar
  12. 12.
    Cane DE, Yang CC (1985) Nargenicin biosynthesis: late stage oxidations and absolute configuration. J Antibiot 38:423–426.  https://doi.org/10.7164/antibiotics.38.423 Google Scholar
  13. 13.
    Celmer WD, Chmurny GN, Moppett CE, Ware RS, Watts PT, Whipple EB (1980) Structure of natural antibiotic CP-47444. J Am Chem Soc 102:4203–4209.  https://doi.org/10.1021/ja00532a036 Google Scholar
  14. 14.
    Chaudhary AK, Dhakal D, Sohng JK (2013) An insight into the “-omics” based engineering of streptomycetes for secondary metabolite overproduction. Biomed Res Int 2013:968518.  https://doi.org/10.1155/2013/968518 Google Scholar
  15. 15.
    Cheng ZH, Yu BY, Cordell GA, Qiu SX (2004) Biotransformation of quinovic acid glycosides by microbes: direct conversion of the ursane to the oleanane triterpene skeleton by Nocardia sp. NRRL 5646. Org Lett 6:3163–3165.  https://doi.org/10.1021/ol048787b Google Scholar
  16. 16.
    Chiba K, Hoshino Y, Ishino K, Kogure T, Mikami Y, Uehara Y, Ishikawa J (2007) Construction of a pair of practical Nocardia-Escherichia coli shuttle vectors. Jpn J Infect Dis. 60:45–47Google Scholar
  17. 17.
    Choi KY, Kim TJ, Koh SK, Roh CH, Pandey BP, Lee N, Kim BG (2009) A-ring ortho-specific monohydroxylation of daidzein by cytochrome P450 s of Nocardia farcinica IFM10152. Biotechnol J 4:1586–1595.  https://doi.org/10.1002/biot.200900157 Google Scholar
  18. 18.
    Conville PS, Fischer SH, Cartwright CP, Witebsky FG (2000) Identification of Nocardia species by restriction endonuclease analysis of an amplified portion of the 16S rRNA gene. J Clin Microbiol 38:158–164Google Scholar
  19. 19.
    Davidsen JM, Townsend CA (2009) Identification and characterization of NocR as a positive transcriptional regulator of the β-lactam nocardicin A in Nocardia uniformis. J Bacteriol 191:1066–1077Google Scholar
  20. 20.
    Davidsen JM, Townsend CA (2012) In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A. Chem Biol 19:297–306.  https://doi.org/10.1016/j.chembiol.2011.10.020 Google Scholar
  21. 21.
    Demain AL, Vaishnav P (2011) Natural products for cancer chemotherapy. Microb Biotechnol 4:687–699.  https://doi.org/10.1111/j.1751-7915.2010.00221.x Google Scholar
  22. 22.
    Dhakal D, Chaudhary AK, Yi JS, Pokhrel AR, Shrestha B, Parajuli P, Shrestha A, Yamaguchi T, Jung HJ, Kim SY, Kim BG (2016) Enhanced production of nargenicin A1 and creation of a novel derivative using a synthetic biology platform. Appl Microbiol Biotechnol 100:9917–9931.  https://doi.org/10.1007/s00253-016-7705-3 Google Scholar
  23. 23.
    Dhakal D, Kumar Jha A, Pokhrel A, Shrestha A, Sohng JK (2016) Genetic manipulation of Nocardia species. Curr Protoc Microbiol. 2016:10F.2.1-18.  https://doi.org/10.1002/9780471729259.mc10f02s40 Google Scholar
  24. 24.
    Dhakal D, Le TT, Pandey RP, Jha AK, Gurung R, Parajuli P, Pokhrel AR, Yoo JC, Sohng JK (2015) Enhanced production of nargenicin A1 and generation of novel glycosylated derivatives. Appl Biochem Biotechnol 175:2934–2949.  https://doi.org/10.1007/s12010-014-1472-3 Google Scholar
  25. 25.
    Dhakal D, Pokhrel AR, Shrestha B, Sohng JK (2017) Marine rare actinobacteria: isolation, characterization, and strategies for harnessing bioactive compounds. Front Microbiol. 8:1106.  https://doi.org/10.3389/fmicb.2017.01106 Google Scholar
  26. 26.
    Dhakal D, Sohng JK (2015) Commentary: toward a new focus in antibiotic and drug discovery from the Streptomyces arsenal. Front Microbiol. 6:727.  https://doi.org/10.3389/fmicb.2015.00727 Google Scholar
  27. 27.
    Dhakal D, Sohng JK (2015) Laboratory maintenance of Nocardia species. Curr Protoc Microbiol. 39:10F.1.1-8.  https://doi.org/10.1002/9780471729259.mc10f01s39 Google Scholar
  28. 28.
    Dhakal D, Sohng JK (2017) Coalition of biology and chemistry for ameliorating antimicrobial drug discovery. Front Microbiol. 8:734.  https://doi.org/10.3389/fmicb.2017.00734 Google Scholar
  29. 29.
    Dye C (2014) After 2015: infectious diseases in a new era of health and development. Philos Trans R Soc Lond B Biol Sci 369:20130426.  https://doi.org/10.1098/rstb.2013.0426 Google Scholar
  30. 30.
    El Sayed KA (1998) Microbial biotransformation of veratramine. J Nat Prod 61:149–151Google Scholar
  31. 31.
    El-Gendy MM, Hawas UW, Jaspars M (2008) Novel bioactive metabolites from a marine derived bacterium Nocardia sp. ALAA 2000. J Antibiot 61:379–386.  https://doi.org/10.1038/ja.2008.53 Google Scholar
  32. 32.
    Feng X, Zou Z, Fu S, Sun L, Su Z, Sun DA (2010) Microbial oxidation and glucosidation of echinocystic acid by Nocardia corallina. J Mol Cat B: Enz. 66:219–223Google Scholar
  33. 33.
    Gao F, Zhang JM, Wang ZG, Peng W, Hu HL, Fu CM (2013) Biotransformation, a promising technology for anti-cancer drug development. Asian Pac J Cancer Prev 14:5599–5608Google Scholar
  34. 34.
    Gao X, Lu Y, Xing Y, Ma Y, Lu J, Bao W, Wang Y, Xi T (2012) A novel anticancer and antifungus phenazine derivative from a marine actinomycete BM-17. Microbiol Res 167:616–622Google Scholar
  35. 35.
    Gbewonyo K, Buckland BC, Lilly MD (1991) Development of a large-scale continuous substrate feed process for the biotransformation of simvastatin by Nocardia sp. Biotechnol Bioeng 37:1101–1107Google Scholar
  36. 36.
    Genilloud O (2017) Actinomycetes: still a source of novel antibiotics. Nat Prod Rep 34:1203–1232.  https://doi.org/10.1039/c7np00026j Google Scholar
  37. 37.
    Goodfellow M (1992) The family Nocardiaceae. In: Balows A, Truper HG, Dworkin M, Harder W, Scheifer K-H (eds) The prokaryotes. Springer, New York, pp 1188–1212Google Scholar
  38. 38.
    Goodfellow M, Kämpfer P, Busse HJ, Trujillo ME, Suzuki K, Ludwig W, Whitman WB (2012) Bergey’s manual of systematic bacteriology, vol Five, 2nd edn. Springer, New YorkGoogle Scholar
  39. 39.
    Gunsior M, Breazeale SD, Lind AJ, Ravel J, Janc JW, Townsend CA (2004) The biosynthetic gene cluster for a monocyclic β-lactam antibiotic, nocardicin A. Chem Biol 11:927–938.  https://doi.org/10.1016/j.chembiol.2004.04.012 Google Scholar
  40. 40.
    Hahn V, Sünwoldt K, Mikolasch A, Schauer F (2013) Two different primary oxidation mechanisms during biotransformation of thymol by gram-positive bacteria of the genera Nocardia and Mycobacterium. Appl Microbiol Biotechnol 97:1289–1297.  https://doi.org/10.1007/s00253-012-4293-8 Google Scholar
  41. 41.
    Hara S, Ishikawa N, Hara Y, Nehira T, Sakai K, Gonoi T, Ishibashi M (2017) Nabscessins A and B, Aminocyclitol Derivatives from Nocardia abscessus IFM 10029T. J Nat Prod 80:565–568.  https://doi.org/10.1021/acs.jnatprod.6b00935 Google Scholar
  42. 42.
    Hashimoto M, Komori T, Kamiya T (1976) Nocardicin A, a new monocyclic β-lactam antibiotic. II. Structure determination of nocardicins A and B. J Antibiot 29:890–901Google Scholar
  43. 43.
    Hayashi Y, Matsuura N, Toshima H, Itoh N, Ishikawa J, Mikami Y, Dairi T (2008) Cloning of the gene cluster responsible for the biosynthesis of brasilicardin A, a unique diterpenoid. J Antibiot 61:164–174.  https://doi.org/10.1038/ja.2008.126 Google Scholar
  44. 44.
    Hegazy MEF, Mohamed TA, ElShamy AI, Abou-El-Hamd HM, Mahalel UA, Reda EH, Shaheen AM, Tawfik WA, Shahat AA, Shams KA, Abdel-Azim NS (2015) Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: a review. J Adv Res 6:17–33.  https://doi.org/10.1016/j.jare.2014.11.009 Google Scholar
  45. 45.
    Hoshino Y, Chiba K, Ishino K, Fukai T, Igarashi Y, Yazawa K, Mikami Y, Ishikawa J (2011) Identification of nocobactin NA biosynthetic gene clusters in Nocardia farcinica. J Bacteriol 193:441–448.  https://doi.org/10.1128/JB.00897-10 Google Scholar
  46. 46.
    Hoshino Y, Mukai A, Yazawa K, Uno J, Ishikawa J, Ando A, Fukai T, Mikami Y (2004) Transvalencin A, a thiazolidine zinc complex antibiotic produced by a clinical isolate of Nocardia transvalensis. J Antibiot 57(12):797–802.  https://doi.org/10.7164/antibiotics.57.803 Google Scholar
  47. 47.
    Hosoda J, Tani N, Konomi T, Ohsawa S, Aoki H, Imanaka H (1977) Incorporation of 14C-amino acids into nocardicin A by growing cells. Biosci Biotechnol Biochem 41:2007–2012.  https://doi.org/10.1080/00021369.1977.10862798 Google Scholar
  48. 48.
    Hosokawa S, Seki M, Fukuda H, Tatsuta K (2006) Total synthesis of an antitubercular lactone antibiotic, (+)-tubelactomicin A. Tetrahedron Lett 47:2439–2442.  https://doi.org/10.1016/j.tetlet.2006.01.140 Google Scholar
  49. 49.
    Igarashi M, Hayashi C, Homma Y, Hattori S, Kinoshita N, Hamada M, Takeuchi T (2000) Tubelactomicin A, a novel 16-membered lactone antibiotic, from Nocardia sp. I. Taxonomy, production, isolation and biological properties. J Antibiot 53:1096–1101.  https://doi.org/10.7164/antibiotics.53.1096 Google Scholar
  50. 50.
    Ikeda Y, Furumai T, Igarashi Y (2005) Nocardimicins G, H and I, siderophores with muscarinic M3 receptor binding inhibitory activity from Nocardia nova JCM 6044. J Antibiot 58:566–572.  https://doi.org/10.1038/ja.2005.77 Google Scholar
  51. 51.
    Ikeda Y, Nonaka H, Furumai T, Onaka H, Igarashi Y (2005) Nocardimicins A, B, C, D, E, and F, siderophores with muscarinic M3 receptor inhibiting activity from Nocardia sp. TP-A0674. J Nat Prod 68:1061–1065.  https://doi.org/10.1021/np050091j Google Scholar
  52. 52.
    Imai T, Yazawa K, Tanaka Y, Mikami Y, Kudo T, Suzuki K, Ando A, Nagata Y, Graefe U (1997) Productivity of antimicrobial substance in pathogenic actinomycetes Nocardia brasiliensis. Microbiol Cult Coll 13:103–108Google Scholar
  53. 53.
    Ishikawa J, Yamashita A, Mikami Y, Hoshino Y, Kurita H, Hotta K, Shiba T, Hattori M (2004) The complete genomic sequence of Nocardia farcinica IFM 10152. Proc Natl Acad Sci USA 101:14925–14930.  https://doi.org/10.1073/pnas.0406410101 Google Scholar
  54. 54.
    Itoh J, Miyadoh S (1992) SF2457, a new antibiotic related to amicetin. J Antibiot 45:846–853Google Scholar
  55. 55.
    Jha AK, Dhakal D, Van PT, Pokhrel AR, Yamaguchi T, Jung HJ, Yoon YJ, Sohng JK (2015) Structural modification of herboxidiene by substrate-flexible cytochrome P450 and glycosyltransferase. Appl Microbiol Biotechnol 99:3421–3431.  https://doi.org/10.1007/s00253-015-6431-6 Google Scholar
  56. 56.
    Jung ME, Chamberlain BT, Koch P, Niazi KR (2015) Synthesis and bioactivity of a brasilicardin A analogue featuring a simplified core. Org Lett 17:3608–3611.  https://doi.org/10.1021/acs.orglett.5b01712 Google Scholar
  57. 57.
    Just-Baringo X, Albericio F, Álvarez M (2014) Thiopeptide antibiotics: retrospective and recent advances. Marine Drugs. 12:317–351.  https://doi.org/10.3390/md12010317 Google Scholar
  58. 58.
    Kamiya T (1977) Studies on the new monocyclic β-lactam antibiotics, nocardicins. In: Proceedings of international symposium of the chemical society, J. Elks, ed. (London), pp 281–294Google Scholar
  59. 59.
    Katz L, Baltz RH (2016) Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43:155–176Google Scholar
  60. 60.
    Katz L, Chen YY, Gonzalez R, Peterson TC, Zhao H, Baltz RH (2018) Synthetic biology advances and applications in the biotechnology industry: a perspective. J Ind Microbiol Biotechnol 7:449–461Google Scholar
  61. 61.
    Kavitha A, Prabhakar P, Vijayalakshmi M, Venkateswarlu Y (2009) Production of bioactive metabolites by Nocardia levis MK-VL_113. Lett Appl Microbiol 49:484–490.  https://doi.org/10.1111/j.1472-765X.2009.02697.x Google Scholar
  62. 62.
    Kawada M, Inoue H, Ohba SI, Hatano M, Amemiya M, Hayashi C, Usami I, Abe H, Watanabe T, Kinoshita N, Igarashi M (2013) Intervenolin, a new antitumor compound with anti-Helicobacter pylori activity, from Nocardia sp. ML96-86F2. J Antibiot 66:543–548.  https://doi.org/10.1038/ja.2013.42 Google Scholar
  63. 63.
    Kelly WL, Townsend CA (2002) Role of the cytochrome P450 NocL in nocardicin A biosynthesis. J Am Chem Soc 124:8186–8187.  https://doi.org/10.1021/ja025926g Google Scholar
  64. 64.
    Kelly WL, Townsend CA (2005) Mutational analysis of nocK and nocL in the nocardicin a producer Nocardiauniformis. J Bacteriol 187:739–746.  https://doi.org/10.1128/JB.187.2.739-746.2005 Google Scholar
  65. 65.
    Kelly WL, Townsend CA (2004) Mutational analysis and characterization of nocardicin C-9′ epimerase. J Biol Chem 279:38220–38227.  https://doi.org/10.1074/jbc.M405450200 Google Scholar
  66. 66.
    Kobayashi JI, Tsuda M, Nemoto A, Tanaka Y, Yazawa K, Mikami Y (1997) Brasilidine A, a new cytotoxic isonitrile-containing indole alkaloid from the actinomycete Nocardia brasiliensis. J Nat Prod 60:719–720.  https://doi.org/10.1021/np970132e Google Scholar
  67. 67.
    Kojo H, Mine Y, Nishida M, Goto S, Kuwahara S (1988) Nature of monocyclic β-lactam antibiotic nocardicin A to β-lactamases. Microbiol Immunol 32:119–130Google Scholar
  68. 68.
    Koju D, Maharjan S, Dhakal D, Yoo JC, Sohng JK (2012) Effect of different biosynthetic precursors on the production of nargenicin A1 from metabolically engineered Nocardia sp. CS682. J Microbiol Biotechnol 22:1127–1132Google Scholar
  69. 69.
    Komaki H, Ichikawa N, Hosoyama A, Takahashi-Nakaguchi A, Matsuzawa T, Suzuki KI, Fujita N, Gonoi T (2014) Genome based analysis of type-I polyketide synthase and nonribosomal peptide synthetase gene clusters in seven strains of five representative Nocardia species. BMC Genom. 15:323.  https://doi.org/10.1186/1471-2164-15-323 Google Scholar
  70. 70.
    Komatsu K, Tsuda M, Shiro M, Tanaka Y, Mikami Y, Kobayashi J (2004) Brasilicardins B-D, new tricyclic terpenoids from actinomycete Nocardia brasiliensis. Bioorg Med Chem 12:5545–5551.  https://doi.org/10.1016/j.bmc.2004.08.007 Google Scholar
  71. 71.
    Kumagai K, Fukui A, Tanaka S, Ikemoto M, Moriguchi K, Nabeshima S (1993) PC-766B, a new macrolide antibiotic produced by Nocardia brasiliensis. II. Isolation, physico-chemical properties and structure elucidation. J Antibiot 46:1139–1144Google Scholar
  72. 72.
    Kumagai K, Taya K, Fukui A, Fukasawa M, Fukui M, Nabeshima S (1993) PC-766B, a new macrolide antibiotic produced by Nocardia brasiliensis. I. Taxonomy, fermentation and biological activity. J Antibiot 46:972–978Google Scholar
  73. 73.
    Kunimoto T, Sawa T, Wakashiro T, Hori M, Umezawa H (1971) Biosynthesis of the formycin family. J Antibiot 24:253–258.  https://doi.org/10.7164/antibiotics.24.253 Google Scholar
  74. 74.
    Lee IS, ElSohly HN, Croom EM, Hufford CD (1989) Microbial metabolism studies of the antimalarial sesquiterpene artemisinin. J Nat Prod 52:337–341Google Scholar
  75. 75.
    Leet JE, Li W, Ax HA, Matson JA, Huang S, Huang R, Cantone JL, Drexler D, Dalterio RA, Lam KS (2003) Nocathiacins, New Thiazolyl Peptide Antibiotics from Nocardia sp. J Antibiot 56:232–242.  https://doi.org/10.7164/antibiotics.56.232 Google Scholar
  76. 76.
    Leipold D, Wünsch G, Schmidt M, Bart HJ, Bley T, Neuhaus HE, Bergmann H, Richling E, Muffler K, Ulber R (2010) Biosynthesis of ursolic acid derivatives by microbial metabolism of ursolic acid with Nocardia sp. Strains-Proposal of new biosynthetic pathways. Process Biochem 45:1043–1051.  https://doi.org/10.1016/j.procbio.2010.03.013 Google Scholar
  77. 77.
    Li W, Leet JE, Ax HA, Gustavson DR, Brown DM, Turner L, Brown K, Clark J, Yang H, Fung-Tomc J, Lam KS (2003) Nocathiacins, new thiazolyl peptide antibiotics from Nocardia sp. J Antibiot. 56:226–231.  https://doi.org/10.7164/antibiotics.56.226 Google Scholar
  78. 78.
    Li W, Yang X, Yang Y, Qin S, Li Q, Zhao L, Ding Z (2015) A new natural nucleotide and other antibacterial metabolites from an endophytic Nocardia sp. Nat Prod Res 29:132–136Google Scholar
  79. 79.
    Li Y, Han N, Gao N, Xu R, Sun C, Li D, He Q (2010) Induction of apoptosis by the angucyclinone antibiotic chemomicin in human tumor cells. Onco Rep. 23:477–483Google Scholar
  80. 80.
    Liao R, Duan L, Lei C, Pan H, Ding Y, Zhang Q, Chen D, Shen B, Yu Y, Liu W (2009) Thiopeptide biosynthesis featuring ribosomally synthesized precursor peptides and conserved posttranslational modifications. Chem Biol 16:141–147.  https://doi.org/10.1016/j.chembiol.2009.01.007 Google Scholar
  81. 81.
    Liu X, Che R, Xi D, Me M, Zo J, Che X, Dai J (2012) Microbial transformations of taxadienes and the multi-drug resistant tumor reversal activities of the metabolites. Tetrahedron 68:9539–9549.  https://doi.org/10.1016/j.tet.2012.09.091 Google Scholar
  82. 82.
    Ludwig B, Geib D, Haas C, Steingroewer J, Bley T, Muffler K, Ulber R (2015) Whole-cell biotransformation of oleanolic acid by free and immobilized cells of Nocardia iowensis: characterization of new metabolites. Eng Life Sci 15:108–115.  https://doi.org/10.1002/elsc.201400121 Google Scholar
  83. 83.
    Luo Q, Hiessl S, Poehlein A, Daniel R, Steinbüchel A (2014) Insights into the microbial degradation of rubber and gutta-percha by analysis of the complete genome of Nocardia nova SH22a. Appl Environ Microbiol 80:3895–3907.  https://doi.org/10.1128/AEM.00473-14 Google Scholar
  84. 84.
    Luo Q, Hiessl S, Steinbüchel A (2014) Functional diversity of Nocardia in metabolism. Environ Microbiol 16:29–48.  https://doi.org/10.1111/1462-2920.12221 Google Scholar
  85. 85.
    Luo Y, Enghiad B, Zhao H (2016) New tools for reconstruction and heterologous expression of natural product biosynthetic gene clusters. Nat Prod Rep 33:174–182.  https://doi.org/10.1039/c5np00085h Google Scholar
  86. 86.
    Maatooq GT, Rosazza JP (2005) Metabolism of daidzein by Nocardia species NRRL 5646 and Mortierella isabellina ATCC 38063. Phytochemistry 66:1007–1011.  https://doi.org/10.1016/j.phytochem.2005.03.013 Google Scholar
  87. 87.
    Maeda A, Nagai H, Yazawa K, Tanaka Y, Imai T, Mikami Y, Kuramochi T, Yamazaki C (1994) Three new reduced anthracycline related compounds from pathogenic Nocardia brasiliensis. J Antibiot 47:976–981Google Scholar
  88. 88.
    Maeda A, Yazawa K, Mikami Y, Ishibashi M, Kobayashi JI (1992) The producer and biological activities of SO-075R1, a new mutactimycin group antibiotic. J Antibiot 45:1848–1852.  https://doi.org/10.7164/antibiotics.45.1848 Google Scholar
  89. 89.
    Maharjan S, Aryal N, Bhattarai S, Koju D, Lamichhane J, Sohng JK (2012) Biosynthesis of the nargenicin A1 pyrrole moiety from Nocardia sp. CS682. Appl Microbiol Biotechnol 93:687–696.  https://doi.org/10.1007/s00253-011-3567-x Google Scholar
  90. 90.
    Maharjan S, Koju D, Lee HC, Yoo JC, Sohng JK (2012) Metabolic engineering of Nocardia sp. CS682 for enhanced production of nargenicin A1. Appl Biochem Biotechnol 166:805–817.  https://doi.org/10.1007/s12010-011-9470-1 Google Scholar
  91. 91.
    McNeil MM, Brown JM (1994) The medically important aerobic actinomycetes: epidemiology and microbiology. Clin Microbiol Rev 7:357–4173Google Scholar
  92. 92.
    McTaggart LR, Richardson SE, Witkowska M, Zhang SX (2010) Phylogeny and identification of Nocardia species on the basis of multilocus sequence analysis. J Clin Microbiol 48:4525–4533Google Scholar
  93. 93.
    Mikami Y, Komaki H, Imai T, Yazawa K, Nemoto A, Tanaka Y, Gräefe U (2000) A new antifungal macrolide component, brasilinolide B, produced by Nocardia brasiliensis. J Antibiot 53:70–74.  https://doi.org/10.7164/antibiotics.53.70 Google Scholar
  94. 94.
    Mikami Y, Yazawa K, Nemoto A, Komaki H, Tanaka Y, Gräfe U (1999) Production of erythromycin E by pathogenic Nocardia brasiliensis. J Antibiot 52:201–202Google Scholar
  95. 95.
    Mikami Y, Yu SF, Yazawa K, Fukushima K, Maeda A, Uno J, Terao K, Saito N, Kubo A, Suzuki KI (1990) A toxic substance produced by Nocardia otitidiscaviarum isolated from cutaneous nocardiosis. Mycopathologia 112:113–118Google Scholar
  96. 96.
    Mikami Y (2007) Biological work on medically important Nocardia species. Actinomycetologica. 21:46–51.  https://doi.org/10.3209/saj.SAJ210107 Google Scholar
  97. 97.
    Momose I, Kinoshita N, Sawa R, Naganawa H, Iinuma H, Hamada M, Takeuchi T (1998) Nothramicin, a new anthracycline antibiotic from Nocardia sp. MJ896-43F17. J Antibiot 51:130–135Google Scholar
  98. 98.
    Motozaki T, Sawamura K, Suzuki A, Yoshida K, Ueki T, Ohara A, Munakata R, Takao KI, Tadano KI (2005) Total synthesis of (+)-tubelactomicin A. 2. Synthesis of the upper-half segment and completion of the total synthesis. Org Lett 7:2265–2267.  https://doi.org/10.1021/ol050763x Google Scholar
  99. 99.
    Motozaki T, Sawamura K, Suzuki A, Yoshida K, Ueki T, Ohara A, Munakata R, Takao KI, Tadano KI (2005) Total synthesis of (+)-tubelactomicin A. 1. Stereoselective synthesis of the lower-half segment by an intramolecular diels-alder approach. Org Lett 7:2261–2264.  https://doi.org/10.1021/ol0507625 Google Scholar
  100. 100.
    Mukai A, Fukai T, Hoshino Y, Yazawa K, Harada KI, Mikami Y (2009) Nocardithiocin, a novel thiopeptide antibiotic, produced by pathogenic Nocardia pseudobrasiliensis IFM 0757. J Antibiot 62:613–619.  https://doi.org/10.1038/ja.2009.90 Google Scholar
  101. 101.
    Mukai A, Fukai T, Matsumoto Y, Ishikawa J, Hoshino Y, Yazawa K, Harada KI, Mikami Y (2006) Transvalencin Z, a new antimicrobial compound with salicylic acid residue from Nocardia transvalensis IFM 10065. J Antibiot 59:366–369.  https://doi.org/10.1038/ja.2006.53 Google Scholar
  102. 102.
    Mukai A, Komaki H, Takagi M, Shinya K (2009) Novel siderophore, JBIR-16, isolated from Nocardia tenerifensis NBRC 101015. J Antibiot 62:601–603.  https://doi.org/10.1038/ja.2009.84 Google Scholar
  103. 103.
    Murakami Y, Kato S, Nakajima M, Matsuoka M, Kawai H, Shin-Ya K, Seto H (1996) Formobactin, a novel free radical scavenging and neuronal cell protecting substance from Nocardia sp. J Antibiot 49:839–845.  https://doi.org/10.7164/antibiotics.49.839 Google Scholar
  104. 104.
    Nemoto A, Hoshino Y, Yazawa K, Ando A, Mikami Y, Komaki H, Tanaka Y, Graefe U (2002) Asterobactin, a new siderophore group antibiotic from Nocardia asteroides. J Antibiot 55:593–597.  https://doi.org/10.7164/antibiotics.55.593 Google Scholar
  105. 105.
    Nemoto A, Tanaka Y, Karasaki Y, Komaki H, Yazawa K, Mikami Y (1997) Brasiliquinones A, B and C, new benz [alpha] anthraquinone antibiotics from Nocardia brasiliensis. I. Producing strain, isolation and biological activities of the J Antibiot 50:18–21.  https://doi.org/10.7164/antibiotics.50.18 Google Scholar
  106. 106.
    Netzker T, Flak M, Krespach MK, Stroe MC, Weber J, Schroeckh V, Brakhage AA (2018) Microbial interactions trigger the production of antibiotics. Curr Opin Microbiol 45:117–123.  https://doi.org/10.1016/j.mib.2018.04.002 Google Scholar
  107. 107.
    Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79:629–661.  https://doi.org/10.1021/acs.jnatprod.5b01055 Google Scholar
  108. 108.
    Noël A, Ferron S, Rouaud I, Gouault N, Hurvois JP, Tomasi S (2017) Isolation and structure identification of novel brominated diketopiperazines from Nocardia ignorata-a lichen-associated actinobacterium. Molecules 22:371.  https://doi.org/10.3390/molecules22030371 Google Scholar
  109. 109.
    Ochi K, Kikuchi S, Yashima S, Eguchi Y (1976) Biosynthesis of formycin. Incorporation and distribution of labeled compounds into formycin. J Antibiot 29:638–645.  https://doi.org/10.7164/antibiotics.29.638 Google Scholar
  110. 110.
    Osprian I, Steinreiber A, Mischitz M, Faber K (1996) Novel bacterial isolates for the resolution of esters of tertiary alcohols. Biotechnol Lett 18:1331–1334Google Scholar
  111. 111.
    Otani T, Sugimoto Y, Aoyagi Y, Igarashi Y, Furumai T, Saito N, Yamada Y, Asao T, Oki T (2000) New Cdc25B tyrosine phosphatase inhibitors, nocardiones A and B, produced by Nocardia sp. TP-A0248. J Antibiot 53:337–344Google Scholar
  112. 112.
    Painter RE, Adam GC, Arocho M, DiNunzio E, Donald RG, Dorso K, Genilloud O, Gill C, Goetz M, Hairston NN, Murgolo N (2015) Elucidation of DnaE as the antibacterial target of the natural product, Nargenicin. Chem Biol 22:1362–1373.  https://doi.org/10.1016/j.chembiol.2015.08.015 Google Scholar
  113. 113.
    Patel PV, Ratledge C (1973) Isolation of lipid-soluble compounds that bind ferric ions from Nocardia species. Biochem Soc Trans 1:886–888Google Scholar
  114. 114.
    Peoples AJ, Zhang Q, Millett WP, Rothfeder MT, Pescatore BC, Madden AA, Ling LL, Moore CM (2008) Neocitreamicins I and II, novel antibiotics with activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci. J Antibiot. 61:457–463.  https://doi.org/10.1038/ja.2008.62 Google Scholar
  115. 115.
    Pervaiz I, Ahmad S, Madni MA, Ahmad H, Khaliq FH (2013) Microbial biotransformation: a tool for drug designing. Prikl Biokhim Mikrobiol 49:437–450Google Scholar
  116. 116.
    Qian LW, Zhang J, Liu JH, Yu BY (2009) Direct microbial-catalyzed asymmetric α-hydroxylation of betulonic acid by Nocardia sp. NRRL 5646. Tetrahedron Lett 50:2193–2195.  https://doi.org/10.1016/j.tetlet.2009.02.137 Google Scholar
  117. 117.
    Qian-Cutrone J, Ueki T, Huang S, Mookhtiar KA, Ezekiel R, Kalinowski SS, Brown KS, Golik J, Lowe S, Pirnik DM, Hugill R, Veitch JA, Klohr SE, Whitney JL, Manly SP (1999) Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii. J Antibiot 52:245–255.  https://doi.org/10.7164/antibiotics.52.245 Google Scholar
  118. 118.
    Ratledge C, Snow GA (1974) Isolation and structure of nocobactin NA, a lipid-soluble iron-binding compound from Nocardia asteroides. Biochem J. 139:407–413Google Scholar
  119. 119.
    Reeve AM, Breazeale SD, Townsend CA (1998) Purification, characterization, and cloning of an S-adenosylmethionine- dependent 3-amino-3-carboxypropyltransferase in nocardicin biosynthesis. J Biol Chem 273:30695–30703Google Scholar
  120. 120.
    Roth A, Andrees S, Kroppenstedt RM, Harmsen D, Mauch H (2003) Phylogeny of the genus Nocardia based on reassessed 16S rRNA gene sequences reveals underspeciation and division of strains classified as Nocardia asteroides into three established species and two unnamed taxons. J Clin Microbiol 41:851–856Google Scholar
  121. 121.
    Sakagami H, Ishihara M, Hoshino Y, Ishikawa J, Mikami Y, Fukai T (2005) Cytotoxicity of nocobactins NA-a, NA-b and their ferric complexes assessed by semiempirical molecular orbital method. Vivo 19:277–282Google Scholar
  122. 122.
    Sakai K, Komaki H, Gonoi T (2015) Identification and Functional Analysis of the Nocardithiocin Gene Cluster in Nocardia pseudobrasiliensis. PLoS ONE 10:e0143264.  https://doi.org/10.1371/journal.pone.0143264 Google Scholar
  123. 123.
    Sawa T, Fukagawa Y, Homma I, Wakashiro T, Takeuchi T, Hori M, Komai T (1968) Metabolic conversion of formycin B to formycin A and to oxoformycin B in Nocardia interforma. J Antibiot 21:334–339.  https://doi.org/10.7164/antibiotics.21.334 Google Scholar
  124. 124.
    Schneider K, Rose I, Vikineswary S, Jones AL, Goodfellow M, Nicholson G, Beil W, Süssmuth RD, Fiedler HP (2007) Nocardichelins A and B, siderophores from Nocardia strain acta 3026. J Nat Prod 70(6):932–935.  https://doi.org/10.1021/np060612i Google Scholar
  125. 125.
    Schwarz PN, Buchmann A, Roller L, Kulik A, Gross H, Wohlleben W, Stegmann E (2018) The immunosuppressant brasilicardin: determination of the biosynthetic gene cluster in the heterologous host Amycolatopsis japonicum. Biotechnol J 13:1700527.  https://doi.org/10.1002/biot.201700527 Google Scholar
  126. 126.
    Schwarz PN, Roller L, Kulik A, Wohlleben W, Stegmann E (2018) Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production. Synt Syst Biot. 3:56–63.  https://doi.org/10.1016/j.synbio.2017.12.005 Google Scholar
  127. 127.
    Sharma P, Slathia PS, Somal P, Mehta P (2012) Biotransformation of cholesterol to 1, 4-androstadiene-3, 17-dione (ADD) by Nocardia species. Ann Microbiol. 62:1651–1659Google Scholar
  128. 128.
    Shigemori H, Komaki H, Yazawa K, Mikami Y, Nemoto A, Tanaka Y, Kobayashi JI (1999) Biosynthesis of diterpenoid moiety of brasilicardin A via non-mevalonate pathway in Nocardia brasiliensis. Tetrahedron Lett 40:4353–4354.  https://doi.org/10.1016/S0040-4039(99)00689-9 Google Scholar
  129. 129.
    Shigemori H, Komaki H, Yazawa K, Mikami Y, Nemoto A, Tanaka Y, Sasaki T, In Y, Ishida T, Kobayashi JI (1998) Brasilicardin A. A novel tricyclic metabolite with potent immunosuppressive activity from actinomycete Nocardia brasiliensis. J Org Chem 63:6900–6904.  https://doi.org/10.1021/jo9807114 Google Scholar
  130. 130.
    Shigemori H, Tanaka Y, Yazawa K, Mikami Y, Kobayashi J (1996) Brasilinolide A, new immunosuppressive macrolide from actinomycete Nocardia brasiliensis. Tetrahedron 52:9031–9034.  https://doi.org/10.1016/0040-4020(96)00464-4 Google Scholar
  131. 131.
    Sohng JK, Yamaguchi T, Seong CN, Baik KS, Park SC, Lee HJ, Jang SY, Simkhada JR, Yoo JC (2008) Production, isolation and biological activity of nargenicin from Nocardia sp. CS682. Arch Pharm Res. 31(10):1339–1345.  https://doi.org/10.1007/s12272-001-2115-0 Google Scholar
  132. 132.
    Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416Google Scholar
  133. 133.
    Suenaga K, Kokubo S, Shinohara C, Tsuji T, Uemura D (1999) Structures of amamistatins A and B, novel growth inhibitors of human tumor cell lines from an actinomycete. Tetrahedron Lett 40:1945–1948.  https://doi.org/10.1016/S0040-4039(99)00050-7 Google Scholar
  134. 134.
    Sun CH, Wang Y, Wang Z, Zhou JQ, Jin WZ, You XF, Gao H, Zhao LX, Si SY, Li X (2007) Chemomicin A, a new angucyclinone antibiotic produced by Nocardia mediterranei subsp. kanglensis 1747-64. J Antibiot 60:211–215Google Scholar
  135. 135.
    Suzuki K, Shimizu T, Nakata T (1998) The cholesterol metabolite cholest-4-en-3-one and its 3-oxo derivatives suppress body weight gain, body fat accumulation and serum lipid concentration in mice. Bioorg Med Chem Lett 8:2133–2138Google Scholar
  136. 136.
    Tamura T, Matsuzawa T, Oji S, Ichikawa N, Hosoyama A, Katsumata H, Yamazoe A, Hamada M, Suzuki KI, Gonoi T, Fujita N (2012) A genome sequence-based approach to taxonomy of the genus Nocardia. Antonie Van Leeuwenhoek 102:481–491.  https://doi.org/10.1007/s10482-012-9780-5 Google Scholar
  137. 137.
    Tamura T, Ohji S, Ichikawa N, Hosoyama A, Yamazoe A, Hamada M, Komaki H, Shibata C, Matsuzawa T, Gonoi T, Suzuki KI (2018) Reclassification of Nocardia species based on whole genome sequence and associated phenotypic data. J Antibiot 71:633–641.  https://doi.org/10.1038/s41429-018-0043-1 Google Scholar
  138. 138.
    Tanaka Y, Grafe U, Yazawak K, Mikami Y, Ritzau M (1997) Nocardicyclins A and B: new anthracycline antibiotics produced by Nocardia pseudobrasiliensis. J Antibiot 50:822–827Google Scholar
  139. 139.
    Tanaka Y, Komaki H, Yazawa K, Mikami Y, Nemoto A, Tojyo T, Kadowaki K, Shigemori H, Kobayashi JI (1997) Brasilinolide A, a new macrolide antibiotic produced by Nocardia brasiliensis: producing strain, isolation and biological activity. J Antibiot 50:1036–1041.  https://doi.org/10.7164/antibiotics.50.1036 Google Scholar
  140. 140.
    Thuan NH, Dhakal D, Pokhrel AR, Chu LL, Van Pham TT, Shrestha A, Sohng JK (2018) Genome-guided exploration of metabolic features of Streptomyces peucetius ATCC 27952: past, current, and prospect. Appl Microbiol Biotech. 102:4355–4370.  https://doi.org/10.1007/s00253-018-8957-x Google Scholar
  141. 141.
    Tong Y, Charusanti P, Zhang L, Weber T, Lee SY (2015) CRISPR-Cas9 based engineering of actinomycetal genomes. ACS Synth Biol. 4:1020–1029.  https://doi.org/10.1021/acssynbio.5b00038 Google Scholar
  142. 142.
    Townsend CA, Brown AM (1981) Biosynthetic studies of nocardicin A. J Am Chem Soc 103:2873–2874.  https://doi.org/10.1021/ja00400a069 Google Scholar
  143. 143.
    Townsend CA, Brown AM (1982) Nocardicin A biosynthesis: stereochemical course of monocyclic. Beta-lactam formation. J Am Chem Soc 104:1748–1750.  https://doi.org/10.1021/ja00370a056 Google Scholar
  144. 144.
    Townsend CA, Brown AM (1983) Nocardicin A: biosynthetic experiments with amino acid precursors. J Am Chem Soc 105:913–918.  https://doi.org/10.1021/ja307710d Google Scholar
  145. 145.
    Townsend CA, Brown AM, Nguyen LT (1983) Nocardicin A: stereochemical and biomimetic studies of monocyclic β-lactam formation. J Am Chem Soc 105:919–927.  https://doi.org/10.1021/ja00342a047 Google Scholar
  146. 146.
    Townsend CA, Salituro GM (1984) Fate of [15 N]-p-hydroxyphenyl) glycine in nocardicin a biosynthesis. J Chem Soc Chem Commun.  https://doi.org/10.1039/c39840001631 Google Scholar
  147. 147.
    Tsuda M, Nemoto A, Komaki H, Tanaka Y, Yazawa K, Mikami Y, Kobayashi JI (1997) Nocarasins A–C and brasiliquinone D, new metabolites from the actinomycete Nocardia brasiliensis. J Nat Prod 62:1640–1642.  https://doi.org/10.1021/np990265v Google Scholar
  148. 148.
    Tsuda M, Sato H, Tanaka Y, Yazawa G, Mikami Y, Sasaki T, Kobayashi JI (1996) Brasiliquinones A-C, new cytotoxic benz[α]anthraquinones with an ethyl group at C-3 from actinomycete Nocardia brasiliensis. J Chem Soc Perkin Trans 1:1773–1775.  https://doi.org/10.1039/P19960001773 Google Scholar
  149. 149.
    Tsuda M, Yamakawa M, Oka S, Tanaka Y, Hoshino Y, Mikami Y, Sato A, Fujiwara H, Ohizumi Y, Kobayashi JI (2005) Brasilibactin A, a cytotoxic compound from actinomycete Nocardia brasiliensis. J Nat Prod 68:462–464.  https://doi.org/10.1021/np0496385 Google Scholar
  150. 150.
    Tsukamoto M, Murooka K, Nakajima S, Abe S, Suzuki H, Hirano K, Kondo H, Kojiri K, Suda H (1997) BE-32030 A, B, C, D and E, new antitumor substances produced by Nocardia sp. A32030. J Antibiot 50:815–821.  https://doi.org/10.7164/antibiotics.50.815 Google Scholar
  151. 151.
    Venisetty RK, Ciddi V (2003) Application of microbial biotransformation for the new drug discovery using natural drugs as substrates. Curr Pharm Biotechnol 4:153–167Google Scholar
  152. 152.
    Vera-Cabrera L, Ortiz-Lopez R, Elizondo-Gonzalez R, Perez-Maya AA, Ocampo-Candiani J (2012) Complete genome sequence of Nocardia brasiliensis HUJEG-1. J Bacteriol 19436:2761–2762.  https://doi.org/10.1371/journal.pone.0065425 Google Scholar
  153. 153.
    Wiebach V, Mainz A, Siegert MJ, Jungmann NA, Lesquame G, Tirat S, Dreux-Zigha A, Aszodi J, Le Beller D, Süssmuth RD (2018) The anti-staphylococcal lipolanthines are ribosomally synthesized lipopeptides. Nat Chem Biol 14:652–654.  https://doi.org/10.1038/s41589-018-0068-6 Google Scholar
  154. 154.
    Wohlleben W, Mast Y, Muth G, Röttgen M, Stegmann E, Weber T (2012) Synthetic biology of secondary metabolite biosynthesis in actinomycetes: engineering precursor supply as a way to optimize antibiotic production. FEBS Lett 586:2171–2176.  https://doi.org/10.1016/j.febslet.2012.04.025 Google Scholar
  155. 155.
    Wyche TP, Hou Y, Vazquez-Rivera E, Braun D, Bugni TS (2012) Peptidolipins B-F, antibacterial lipopeptides from an ascidian-derived Nocardia sp. J Nat Prod 75:735–740.  https://doi.org/10.1021/np300016r Google Scholar
  156. 156.
    Yasuike M, Nishiki I, Iwasaki Y, Nakamura Y, Fujiwara A, Shimahara Y, Kamaishi T, Yoshida T, Nagai S, Kobayashi T, Katoh M (2017) Analysis of the complete genome sequence of Nocardia seriolae UTF1, the causative agent of fish nocardiosis: the first reference genome sequence of the fish pathogenic Nocardia species. PLoS One 12:e0173198.  https://doi.org/10.1371/journal.pone.0173198 Google Scholar
  157. 157.
    Zerikly M, Challis GL (2009) Strategies for the discovery of new natural products by genome mining. ChemBioChem 10:625–633.  https://doi.org/10.1002/cbic.200800389 Google Scholar
  158. 158.
    Zhang J, Cheng ZH, Yu BY, Cordell GA, Qiu SX (2005) Novel biotransformation of pentacyclic triterpenoid acids by Nocardia sp. NRRL 5646. Tetrahedron Lett 46:2337–2340.  https://doi.org/10.1016/j.tetlet.2005.01.155 Google Scholar
  159. 159.
    Zhang J, Sun Y, Liu JH, Yu BY, Xu Q (2007) Microbial transformation of three bufadienolides by Nocardia sp. and some insight for the cytotoxic structure–activity relationship (SAR). Bioorg Med Chem Lett 17:6062–6065.  https://doi.org/10.1016/j.bmcl.2007.09.065 Google Scholar
  160. 160.
    Zhang MM, Wong FT, Wang Y, Luo S, Lim YH, Heng E, Yeo WL, Cobb RE, Enghiad B, Ang EL, Zhao H (2017) CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol 13:607–609.  https://doi.org/10.1038/nchembio.2341 Google Scholar
  161. 161.
    Zoropogui A, Pujic P, Normand P, Barbe V, Belli P, Graindorge A, Roche D, Vallenet D, Mangenot S, Boiron P, Rodriguez-Nava V (2013) The Nocardia cyriacigeorgica GUH-2 genome shows ongoing adaptation of an environmental Actinobacteria to a pathogen’s lifestyle. BMC Genom 14(1):286.  https://doi.org/10.1186/1471-2164-14-286 Google Scholar

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© Society for Industrial Microbiology and Biotechnology 2019

Authors and Affiliations

  1. 1.Department of Life Science and Biochemical EngineeringSunMoon UniversityAsan-siRepublic of Korea
  2. 2.Department of BT-Convergent Pharmaceutical EngineeringSunMoon UniversityAsan-siRepublic of Korea

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