Epimerization domain of nonribosomal peptide synthetases (NRPSs); belongs to the Condensation-domain family; Epimerization (E) domains of nonribosomal peptide synthetases (NRPS) flip the chirality of the end amino acid of a peptide being manufactured by the NRPS. E-domains are homologous to the Condensation (C) domains. NRPSs catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. Specialized tailoring NRPS domains such as E-domains greatly increase the range of possible peptide products created by the NRPS machinery. NRPS can use a large variety of acyl monomers (approximately 500 different possible monomer substrates as opposed to the 20 standard amino acids in ribosomal protein synthesis) to construct bioactive secondary metabolites of 2 to 18 units long (with various activities such as antibiotic, antifungal, antitumor and immunosuppression). There are various subtypes of C-domains such as the LCL-type which catalyzes peptide bond formation between two L-amino acids, the DCL-type which links an L-amino acid to the D-amino acid at the end of a growing peptide, starter C-domains which acylate the first amino acid with a beta-hydroxy carboxylic acid, and heterocyclization (Cyc) domains which catalyze both peptide bond formation and cyclization of Cys, Ser, or Thr residues. Typically, an NRPS module consists of an adenylation domain, a peptidyl carrier protein (PCP) domain (also known as thiolation (T) domain) and a C-domain. NRPS modules may also include specialized domains such as the terminal-module thioesterase (Te) domain that releases the product via hydrolysis or macrocyclization and any of various C-domain family members such as the E-domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain. C-domains typically have a conserved HHxxxD motif at the active site; mutations in this motif can abolish or diminish condensation activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 1779797515  37 PLLPIQARFFELDIPERQHWNQALMLKPLQTLDAIHLQAALTALIEQH 84
Cdd:cd19534     3 PLTPIQRWFFEQNLAGRHHFNQSVLLRVPQGLDPDALRQALRALVEHH 50

Condensation domain; This domain is found in many multi-domain enzymes which synthesize peptide antibiotics. This domain catalyzes a condensation reaction to form peptide bonds in non- ribosomal peptide biosynthesis. It is usually found to the carboxy side of a phosphopantetheine binding domain (pfam00550). It has been shown that mutations in the HHXXXDG motif abolish activity suggesting this is part of the active site.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1779797515  32 ISGSLPLLPIQAR--FFELDIPERQHWNQALMLKPLQTLDAIHLQAALTALIEQH 84
Cdd:pfam00668   1 VQDEYPLSPAQKRmwFLEKLEPHSSAYNMPAVLKLTGELDPERLEKALQELINRH 55

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779797515    1 SPKQLFEKQTISQLASVAKLIQKKPAAPVEQISGSLPLLPIQARFFELDIPERQHWNQALMLKPLQTLDAIHLQAALTAL 80
Cdd:PRK12467  2146 TPKDLFQHQTVQSLAAVAQEGDGTVSIDQGPVTGDLPLLPIQQMFFADDIPERHHWNQSVLLEPREALDAELLEAALQAL 2225

                   ....
gi 1779797515   81 IEQH 84
Cdd:PRK12467  2226 LVHH 2229

peptide synthase; Validated

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779797515    1 SPKQLFEKQTISQLASVAKLIQKkPAAPVEQISGSLPLLPIQARFFELDIPERQHWNQALMLKPLQTLDAIHLQAALTAL 80
Cdd:PRK05691  2758 SPRDLFQHQTVQTLAAVATHSEA-AQAEQGPLQGASGLTPIQHWFFDSPVPQPQHWNQALLLEPRQALDPALLEQALQAL 2836

                   ....
gi 1779797515   81 IEQH 84
Cdd:PRK05691  2837 VEHH 2840

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1779797515    2 PKQLFEKQTISQLASVAKLIQKKPAAPVEQISGSLPLLPIQAR----FFELDIPERQHWNQALMLKPLQTLDAIHLQAAL 77
Cdd:PRK12316  2567 LRILFERPTLAAFAASLESGQTSRAPVLQKVTRVQPLPLSHAQqrqwFLWQLEPESAAYHLPSALHLRGVLDQAALEQAF 2646

                   ....*..
gi 1779797515   78 TALIEQH 84
Cdd:PRK12316  2647 DALVLRH 2653

Condensation domain; This domain is found in many multi-domain enzymes which synthesize peptide antibiotics. This domain catalyzes a condensation reaction to form peptide bonds in non- ribosomal peptide biosynthesis. It is usually found to the carboxy side of a phosphopantetheine binding domain (pfam00550). It has been shown that mutations in the HHXXXDG motif abolish activity suggesting this is part of the active site.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1779797515  32 ISGSLPLLPIQAR--FFELDIPERQHWNQALMLKPLQTLDAIHLQAALTALIEQH 84
Cdd:pfam00668   1 VQDEYPLSPAQKRmwFLEKLEPHSSAYNMPAVLKLTGELDPERLEKALQELINRH 55