Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA ‐Specified Leu‐tRNA UUA Molecule

Nucleocidin is one of the very few natural products known to contain fluorine. Mysteriously, the nucleocidin producer Streptomyces calvus ATCC 13382 has not been observed to synthesize the compound since its discovery in 1956. Here, we report that complementation of S. calvus ATCC 13382 with a funct...

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Published inChembiochem : a European journal of chemical biology Vol. 16; no. 17; pp. 2498 - 2506
Main Authors Zhu, Xi Ming, Hackl, Stefanie, Thaker, Maulik N., Kalan, Lindsay, Weber, Claudia, Urgast, Dagmar S., Krupp, Eva M., Brewer, Alyssa, Vanner, Stephanie, Szawiola, Anjuli, Yim, Grace, Feldmann, Jörg, Bechthold, Andreas, Wright, Gerard D., Zechel, David L.
Format Journal Article
LanguageEnglish
Published 01.11.2015
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Abstract Nucleocidin is one of the very few natural products known to contain fluorine. Mysteriously, the nucleocidin producer Streptomyces calvus ATCC 13382 has not been observed to synthesize the compound since its discovery in 1956. Here, we report that complementation of S. calvus ATCC 13382 with a functional bldA ‐encoded Leu‐tRNA UUA molecule restores the production of nucleocidin. Nucleocidin was detected in culture extracts by 19 F NMR spectroscopy, HPLC‐ESI‐MS, and HPLC‐continuum source molecular absorption spectroscopy for fluorine‐specific detection. The molecule was purified from a large‐scale culture and definitively characterized by NMR spectroscopy and high‐resolution MS. The nucleocidin biosynthetic gene cluster was identified by the presence of genes encoding the 5′‐ O ‐sulfamate moiety and confirmed by gene disruption. Two of the genes within the nucleocidin biosynthetic gene cluster contain TTA codons, thus explaining the dependence on bldA and resolving a 60‐year‐old mystery.
AbstractList Nucleocidin is one of the very few natural products known to contain fluorine. Mysteriously, the nucleocidin producer Streptomyces calvus ATCC 13382 has not been observed to synthesize the compound since its discovery in 1956. Here, we report that complementation of S. calvus ATCC 13382 with a functional bldA ‐encoded Leu‐tRNA UUA molecule restores the production of nucleocidin. Nucleocidin was detected in culture extracts by 19 F NMR spectroscopy, HPLC‐ESI‐MS, and HPLC‐continuum source molecular absorption spectroscopy for fluorine‐specific detection. The molecule was purified from a large‐scale culture and definitively characterized by NMR spectroscopy and high‐resolution MS. The nucleocidin biosynthetic gene cluster was identified by the presence of genes encoding the 5′‐ O ‐sulfamate moiety and confirmed by gene disruption. Two of the genes within the nucleocidin biosynthetic gene cluster contain TTA codons, thus explaining the dependence on bldA and resolving a 60‐year‐old mystery.
Author Wright, Gerard D.
Szawiola, Anjuli
Yim, Grace
Hackl, Stefanie
Brewer, Alyssa
Zhu, Xi Ming
Krupp, Eva M.
Urgast, Dagmar S.
Zechel, David L.
Weber, Claudia
Thaker, Maulik N.
Kalan, Lindsay
Feldmann, Jörg
Vanner, Stephanie
Bechthold, Andreas
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  organization: Department of Chemistry Queen's University Chernoff Hall 90 Bader Lane Kingston Ontario K7L 3N6 Canada
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  organization: Department of Chemistry Queen's University Chernoff Hall 90 Bader Lane Kingston Ontario K7L 3N6 Canada
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Cites_doi 10.1021/cr4002879
10.1128/jb.164.1.85-94.1985
10.1038/nchembio706
10.1039/c3ja50086a
10.1016/0378-1119(92)90547-3
10.1128/JB.182.1.135-142.2000
10.1016/j.chembiol.2013.10.001
10.1039/P19930001795
10.1097/00010694-191908000-00001
10.1007/978-94-007-7359-2_16
10.3209/saj.SAJ230205
10.1371/journal.pone.0114722
10.1128/JB.00147-13
10.1021/ac301201y
10.1021/ol702222z
10.1021/cr500209t
10.1098/rsob.130121
10.1016/S0021-9258(18)96807-9
10.7164/antibiotics.37.670
10.1016/j.chembiol.2013.09.006
10.1021/ja01034a046
10.1002/ardp.201500073
10.1073/pnas.31.5.129
10.1039/C4SC03540B
10.1111/j.1365-2958.2011.07795.x
10.1128/JB.187.16.5595-5604.2005
10.1111/j.1365-2958.2010.07455.x
10.1128/MMBR.00054-12
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References e_1_2_7_6_1
e_1_2_7_4_1
e_1_2_7_3_1
e_1_2_7_9_1
e_1_2_7_8_1
e_1_2_7_7_1
Ohnuki T. (e_1_2_7_16_1) 1985; 164
e_1_2_7_19_1
e_1_2_7_18_1
Thomas S. O. (e_1_2_7_5_1) 1956; 1956
e_1_2_7_17_1
e_1_2_7_2_1
e_1_2_7_15_1
e_1_2_7_1_1
e_1_2_7_14_1
e_1_2_7_13_1
e_1_2_7_12_1
e_1_2_7_11_1
e_1_2_7_10_1
e_1_2_7_26_1
e_1_2_7_27_1
e_1_2_7_28_1
Florini J. R. (e_1_2_7_29_1) 1966; 241
e_1_2_7_30_1
e_1_2_7_25_1
e_1_2_7_24_1
e_1_2_7_23_1
e_1_2_7_22_1
e_1_2_7_21_1
e_1_2_7_20_1
References_xml – ident: e_1_2_7_28_1
  doi: 10.1021/cr4002879
– volume: 1956
  start-page: 716
  year: 1956
  ident: e_1_2_7_5_1
  publication-title: Antibiot. Annu.
  contributor:
    fullname: Thomas S. O.
– volume: 164
  start-page: 85
  year: 1985
  ident: e_1_2_7_16_1
  publication-title: J. Bacteriol.
  doi: 10.1128/jb.164.1.85-94.1985
  contributor:
    fullname: Ohnuki T.
– ident: e_1_2_7_30_1
  doi: 10.1038/nchembio706
– ident: e_1_2_7_19_1
  doi: 10.1039/c3ja50086a
– ident: e_1_2_7_27_1
  doi: 10.1016/0378-1119(92)90547-3
– ident: e_1_2_7_12_1
  doi: 10.1128/JB.182.1.135-142.2000
– ident: e_1_2_7_24_1
  doi: 10.1016/j.chembiol.2013.10.001
– ident: e_1_2_7_7_1
  doi: 10.1039/P19930001795
– ident: e_1_2_7_21_1
  doi: 10.1097/00010694-191908000-00001
– ident: e_1_2_7_4_1
  doi: 10.1007/978-94-007-7359-2_16
– ident: e_1_2_7_6_1
  doi: 10.3209/saj.SAJ230205
– ident: e_1_2_7_8_1
  doi: 10.1371/journal.pone.0114722
– ident: e_1_2_7_17_1
  doi: 10.1128/JB.00147-13
– ident: e_1_2_7_18_1
  doi: 10.1021/ac301201y
– ident: e_1_2_7_20_1
  doi: 10.1021/ol702222z
– ident: e_1_2_7_1_1
  doi: 10.1021/cr500209t
– ident: e_1_2_7_25_1
  doi: 10.1098/rsob.130121
– volume: 241
  start-page: 1091
  year: 1966
  ident: e_1_2_7_29_1
  publication-title: J. Biol. Chem.
  doi: 10.1016/S0021-9258(18)96807-9
  contributor:
    fullname: Florini J. R.
– ident: e_1_2_7_3_1
  doi: 10.7164/antibiotics.37.670
– ident: e_1_2_7_13_1
– ident: e_1_2_7_9_1
  doi: 10.1016/j.chembiol.2013.09.006
– ident: e_1_2_7_14_1
  doi: 10.1021/ja01034a046
– ident: e_1_2_7_11_1
  doi: 10.1002/ardp.201500073
– ident: e_1_2_7_22_1
  doi: 10.1073/pnas.31.5.129
– ident: e_1_2_7_2_1
  doi: 10.1039/C4SC03540B
– ident: e_1_2_7_23_1
  doi: 10.1111/j.1365-2958.2011.07795.x
– ident: e_1_2_7_15_1
  doi: 10.1128/JB.187.16.5595-5604.2005
– ident: e_1_2_7_26_1
  doi: 10.1111/j.1365-2958.2010.07455.x
– ident: e_1_2_7_10_1
  doi: 10.1128/MMBR.00054-12
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Title Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA ‐Specified Leu‐tRNA UUA Molecule
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