KEGG   ENZYME: 6.2.2.2
Entry
EC 6.2.2.2                  Enzyme                                 

Name
oxazoline synthase;
cyanobactin heterocyclase;
cyanobactin cyclodehydratase;
patD (gene name);
balhD (gene name);
micD (gene name)
Class
Ligases;
Forming carbon-sulfur bonds;
Amide---thiol ligases
Sysname
[protein]-(L-amino acyl-L-serine) cyclodehydratase (2-oxazoline-forming)
Reaction(IUBMB)
(1) ATP + a [protein]-(L-amino acyl-L-serine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline;
(2) ATP + a [protein]-(L-amino acyl-L-threonine) = ADP + phosphate + a [protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline;
(3) ATP + a [protein]-(L-amino acyl-L-cysteine) = ADP + phosphate + a [protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Substrate
ATP [CPD:C00002];
[protein]-(L-amino acyl-L-serine);
[protein]-(L-amino acyl-L-threonine);
[protein]-(L-amino acyl-L-cysteine)
Product
ADP [CPD:C00008];
phosphate [CPD:C00009];
[protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-2-oxazoline;
[protein]-(S,S)-2-(C-substituted-aminomethyl)-4-acyl-5-methyl-2-oxazoline;
[protein]-(1S,4R)-2-(C-substituted-aminomethyl)-4-acyl-2-thiazoline
Comment
Requires Mg2+. The enzyme, which participates in the biosynthesis of ribosomal peptide natural products (RiPPs), converts L-cysteine, L-serine and L-threonine residues to thiazoline, oxazoline, and methyloxazoline rings, respectively. The enzyme requires two domains - a cyclodehydratase domain, known as a YcaO domain, and a substrate recognition domain (RRE domain) that controls the regiospecificity of the enzyme. The RRE domain can either be fused to the YcaO domain or occur as a separate protein; however both domains are required for activity. The enzyme can process multiple residues within the same substrate peptide, and all enzymes characterized so far follow a defined order, starting with the L-cysteine closest to the C-terminus. The reaction involves phosphorylation of the preceding ribosomal peptide backbone amide bond, forming ADP and a phosphorylated intermediate, followed by release of the phosphate group. In some cases the enzyme catalyses a side reaction in which the phosphorylated intermediate reacts with ADP to form AMP and diphosphate.
History
EC 6.2.2.2 created 2020
Orthology
K24411  oxazoline/thiazoline synthase
Genes
PGB: H744_2c1844
PRR: AT705_20070
PVB: J5X90_21760
MPSY: CEK71_11635
TIG: THII_1452
AQL: BXU06_00280
BMA: BMA0023
BMV: BMASAVP1_A2869
BML: BMA10229_A2214
BMN: BMA10247_2493
BMAL: DM55_418
BMAE: DM78_499
BMAQ: DM76_398
BMAI: DM57_2183
BMAF: DM51_3009
BMAZ: BM44_807
BMAB: BM45_414
BPS: BPSL0600
BPSE: BDL_1405
BPSM: BBQ_2827
BPSD: BBX_3353
BPK: BBK_886
BPSH: DR55_494
BPSA: BBU_1551
BPSO: X996_101
BUT: X994_2115
BTE: BTH_I0517
BTQ: BTQ_539
BTJ: BTJ_1946
BTZ: BTL_3182
BTD: BTI_3187
BTV: BTHA_3465
BTHE: BTN_1530
BTHM: BTRA_60
BTHA: DR62_1717
BTHL: BG87_25
BOK: DM82_26
BOC: BG90_995
BCN: Bcen_5136
BCJ: BCAM0032
BCEO: I35_4032
BAM: Bamb_4992
BCED: DM42_5115
BSEM: WJ12_25405
BSTG: WT74_32040
BUL: BW21_3336
AAV: Aave_3061
AAA: Acav_2221
DAC: Daci_4368
SAT: SYN_00274
BJA: blr4538(blr4538)
MET: M446_3967
MNO: Mnod_4676
MSC: BN69_1551
SHUM: STHU_40390
SWO: Swol_1788
SALB: XNR_3461
SMAL: SMALA_2873
SBH: SBI_06840
SVE: SVEN_6223
SLAU: SLA_3079
MLV: CVS47_02157(ycaO)
LMOI: VV02_06540
TCU: Tcur_2767
AOI: AORI_1830
AMYY: YIM_41055
AORI: SD37_32060
ALO: CRK57519
MAR: MAE_33130
MPK: VL20_3234
CYT: cce_4099
TER: Tery_2355
FTJ: FTUN_1196
PLT: Plut_0880
 » show all
Reference
1  [PMID:20210311]
  Authors
McIntosh JA, Donia MS, Schmidt EW
  Title
Insights into heterocyclization from two highly similar enzymes.
  Journal
J Am Chem Soc 132:4089-91 (2010)
DOI:10.1021/ja9107116
Reference
2  [PMID:22401305]
  Authors
Melby JO, Dunbar KL, Trinh NQ, Mitchell DA
  Title
Selectivity, directionality, and promiscuity in peptide processing from a Bacillus sp. Al Hakam cyclodehydratase.
  Journal
J Am Chem Soc 134:5309-16 (2012)
DOI:10.1021/ja211675n
Reference
3  [PMID:30912640]
  Authors
Ge Y, Czekster CM, Miller OK, Botting CH, Schwarz-Linek U, Naismith JH
  Title
Insights into the Mechanism of the Cyanobactin Heterocyclase Enzyme.
  Journal
Biochemistry 58:2125-2132 (2019)
DOI:10.1021/acs.biochem.9b00084
  Sequence
Other DBs
ExplorEnz - The Enzyme Database: 6.2.2.2
IUBMB Enzyme Nomenclature: 6.2.2.2
ExPASy - ENZYME nomenclature database: 6.2.2.2
BRENDA, the Enzyme Database: 6.2.2.2

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