Production of Antitubercular Depsipeptides via Biosynthetic Engineering of Cinnamoyl Units
Yang, Zhijie; Sun, Changli; Liu, Zhiyong; Liu, Qing; Zhang, Tianyu; Ju, Jianhua; Ma, Junying; Journal of Natural Products  (2020) –; doi:10.1021/acs.jnatprod.0c00194

data_1557922
_publ_section_title
;
 Production of Antitubercular Depsipeptides via Biosynthetic Engineering
 of Cinnamoyl Units
;
_journal_name_full               'Journal of Natural Products'
_journal_paper_doi               10.1021/acs.jnatprod.0c00194
_journal_year                    2020
_chemical_absolute_configuration rm
_chemical_formula_moiety         'C72 H88 N12 O16'
_chemical_formula_sum            'C72 H88 N12 O16'
_chemical_formula_weight         1377.54
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2020-02-22
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 103.722(2)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   12.5668(2)
_cell_length_b                   20.9262(3)
_cell_length_c                   15.2207(2)
_cell_measurement_reflns_used    15804
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      71.9360
_cell_measurement_theta_min      3.6890
_cell_volume                     3888.43(10)
_computing_cell_refinement       'CrysAlisPro 1.171.39.33c (Rigaku OD, 2017)'
_computing_data_collection       'CrysAlisPro 1.171.39.33c (Rigaku OD, 2017)'
_computing_data_reduction        'CrysAlisPro 1.171.39.33c (Rigaku OD, 2017)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD plate'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.988
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \w      3.00  76.00   0.50    3.42    --   45.70 -57.00  90.00  146
  2  \w     26.00 127.00   0.50    3.42    --   45.70  38.00 -60.00  202
  3  \w     94.00 134.00   0.50    3.42    --   45.70  77.00 -30.00   80
  4  \w     59.00 134.00   0.50    3.42    --   45.70  38.00  90.00  150
  5  \w    -44.00 -14.00   0.50    3.42    --   45.70 -57.00  90.00   60
  6  \w     99.00 128.00   0.50    3.42    --   45.70  82.00 150.00   58
  7  \w    -44.00  66.00   0.50    3.42    --   45.70 -77.00 -90.00  220
  8  \w     13.00  98.00   0.50    3.42    --   45.70  38.00  60.00  170
  9  \w    150.00 185.00   0.50   17.80    --  100.10  77.00 -90.00   70
 10  \w     11.00 135.00   0.50   17.80    --  100.10 -82.00  60.00  248
 11  \w    118.00 145.00   0.50   17.80    --  100.10  77.00 -90.00   54
 12  \w     89.00 155.00   0.50   17.80    --  100.10  82.00   0.00  132
 13  \w     13.00 139.00   0.50   17.80    --  100.10 -82.00-150.00  252
 14  \w     66.00 179.00   0.50   17.80    --  100.10  30.00  90.00  226
 15  \w     16.00  56.00   0.50   17.80    --  100.10 -75.00-176.00   80
 16  \w     81.00 108.00   0.50   17.80    --  100.10  61.00-120.00   54
 17  \w    117.00 147.00   0.50   17.80    --  100.10  82.00 -30.00   60
 18  \w    103.00 183.00   0.50   17.80    --  100.10  30.00 -90.00  160
 19  \w     12.00 127.00   0.50   17.80    --  100.10 -61.00-150.00  230
 20  \w     83.00 186.00   0.50   17.80    --  100.10  45.00-120.00  206
 21  \w     76.00 189.00   0.50   17.80    --  100.10  30.00 120.00  226
 22  \w     63.00 115.00   0.50   17.80    --  100.10 -45.00-180.00  104
 23  \w     69.00 171.00   0.50   17.80    --  100.10  30.00  60.00  204
 24  \w     79.00 173.00   0.50   17.80    --  100.10  45.00 150.00  188
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB AFC12 (RINC): Kappa single'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0546561000
_diffrn_orient_matrix_UB_12      0.0235007000
_diffrn_orient_matrix_UB_13      -0.0745361000
_diffrn_orient_matrix_UB_21      -0.0821678000
_diffrn_orient_matrix_UB_22      0.0557339000
_diffrn_orient_matrix_UB_23      -0.0209954000
_diffrn_orient_matrix_UB_31      0.0787959000
_diffrn_orient_matrix_UB_32      0.0419614000
_diffrn_orient_matrix_UB_33      0.0696573000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0326
_diffrn_reflns_av_unetI/netI     0.0375
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.988
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -25
_diffrn_reflns_limit_l_max       18
_diffrn_reflns_limit_l_min       -18
_diffrn_reflns_number            43267
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.974
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.590
_diffrn_reflns_theta_min         3.621
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.693
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.70749
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.33c (Rigaku Oxford Diffraction, 2017)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.177
_exptl_crystal_description       block
_exptl_crystal_F_000             1464
_exptl_crystal_size_max          0.1
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.263
_refine_diff_density_min         -0.204
_refine_diff_density_rms         0.037
_refine_ls_abs_structure_details
;
 Flack x determined using 5445 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.10(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.040
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     952
_refine_ls_number_reflns         15047
_refine_ls_number_restraints     28
_refine_ls_restrained_S_all      1.052
_refine_ls_R_factor_all          0.0526
_refine_ls_R_factor_gt           0.0452
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0778P)^2^+0.2511P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1209
_refine_ls_wR_factor_ref         0.1262
_reflns_Friedel_coverage         0.915
_reflns_Friedel_fraction_full    0.998
_reflns_Friedel_fraction_max     0.958
_reflns_number_gt                12978
_reflns_number_total             15047
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            np0c00194_si_002.cif
_cod_data_source_block           yangzhijie_prea_collect
_cod_original_cell_volume        3888.42(10)
_cod_database_code               1557922
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.966
_shelx_estimated_absorpt_t_min   0.934
_reflns_odcompleteness_completeness 99.97
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, H12 of N12, H9 of N9, H2 of N2, H1 of N1, H5 of N5, H3 of
  N3, H7 of N7, H4 of N4, H11 of N11, H10a of N10, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, H6a of N6, All O(H) groups
2. Restrained distances
 C11-C10 = C73-C10A = C13-C12
 1.34 with sigma of 0.02
 C73-C10A = C11-C10 = C13-C12
 1.34 with sigma of 0.02
 C14-C13 = C14A-C13A
 1.54 with sigma of 0.02
 C13A-C12A
 1.34 with sigma of 0.02
3. Rigid bond restraints
 C12A
 with sigma for 1-2 distances of 0.0002 and sigma for 1-3 distances of 0.0001
 C61
 with sigma for 1-2 distances of 0.0002 and sigma for 1-3 distances of 0.0001
4. Uiso/Uaniso restraints and constraints
Uanis(C63) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C63) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C61) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C12A) \\sim Ueq: with sigma of 0.01 and sigma for terminal atoms of 0.02
Uanis(C4) = Uanis(C4A)
Uanis(C8) = Uanis(C8A)
Uanis(C5) = Uanis(C5A)
Uanis(C9) = Uanis(C9A)
Uanis(C6) = Uanis(C6A)
Uanis(C7) = Uanis(C7A)
Uanis(C10) = Uanis(C10A)
5. Others
 Sof(C4A)=Sof(C9A)=Sof(C8A)=Sof(H8A)=Sof(C7A)=Sof(H7Aa)=Sof(C6A)=Sof(H6Aa)=
 Sof(C5A)=Sof(H5Aa)=Sof(C10A)=Sof(H10c)=Sof(C73)=Sof(H73)=Sof(C12A)=Sof(H12c)=
 Sof(C14A)=Sof(H14d)=Sof(H14e)=Sof(C13A)=Sof(H13A)=1-FVAR(1)
 Sof(C4)=Sof(C9)=Sof(C8)=Sof(H8)=Sof(C7)=Sof(H7a)=Sof(C6)=Sof(H6)=Sof(C5)=
 Sof(H5b)=Sof(C10)=Sof(H10b)=Sof(C11)=Sof(H11a)=Sof(C12)=Sof(H12b)=Sof(C13)=
 Sof(H13)=Sof(C14)=Sof(H14a)=Sof(H14b)=Sof(H14c)=FVAR(1)
 Fixed Sof: H12a(0.40309)
6.a Ternary CH refined with riding coordinates:
 C16(H16), C47(H47), C34(H34), C17(H17), C23(H23), C39(H39), C38(H38),
 C20(H20), C65(H65), C52(H52), C59(H59), C53(H53)
6.b Secondary CH2 refined with riding coordinates:
 C21(H21a,H21b), C24(H24a,H24b), C50(H50a,H50b), C66(H66a,H66b), C35(H35a,
 H35b), C48(H48a,H48b), C49(H49a,H49b), C57(H57a,H57b), C60(H60a,H60b),
 C12(H12a,H12b)
6.c Aromatic/amide H refined with riding coordinates:
 N2(H2), N1(H1), N5(H5), N3(H3), N7(H7), N4(H4), N12(H12), N9(H9), N11(H11),
 C3(H3a), C26(H26), C2(H2a), N10(H10a), C8(H8), C7(H7a), C6(H6), C5(H5b),
 C68(H68), C29(H29), C31(H31), C28(H28), C41(H41), C30(H30), C42(H42), C69(H69),
  C45(H45), C43(H43), C44(H44), C10(H10b), C72(H72), C71(H71), C8A(H8A),
 C7A(H7Aa), C6A(H6Aa), C5A(H5Aa), C10A(H10c), C11(H11a), C13(H13), C73(H73),
 C12A(H12c), C13A(H13A)
6.d Fitted hexagon refined as free rotating group:
 C4(C9,C8,C7,C6,C5), C4A(C9A,C8A,C7A,C6A,C5A)
6.e X=CH2 refined with riding coordinates:
 C14A(H14d,H14e)
6.f Idealised Me refined as rotating group:
 C18(H18a,H18b,H18c), C55(H55a,H55b,H55c), C54(H54a,H54b,H54c), C62(H62a,H62b,
 H62c), C63(H63a,H63b,H63c), C14(H14a,H14b,H14c)
6.g Idealised tetrahedral OH refined as rotating group:
 O10(H10), O5(H5a), N6(H6a), O16(H16a)
;
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.517
_oxdiff_exptl_absorpt_empirical_full_min 0.733