Condensation domain of nonribosomal peptide synthetases (NRPSs); Condensation (C) domains of nonribosomal peptide synthetases (NRPSs) catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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 epimerization (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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVHKQGQWQQYHSDD-WESFGFEVMDLSpmsSGEQLTTMAEISEAQQRSLNLEKGPLISVVFFQL-GD 79
Cdd:cd19534   45 ALVEHHDALRMRFRREDGGWQQRIRGDvEELFRLEVVDLS---SLAQAAAIEALAAEAQSSLDLEEGPLLAAALFDGtDG 121

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308051767  80 AGRLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19534  122 GDRLLLVIHHLVVDGVSWRILLEDLEAAYEQALAG 156

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVHKQGQWQQYHSDD-WESFGFEVMDLSpmsSGEQLTTMAEISEAQQRSLNLEKGPLISVVFFQL-GD 79
Cdd:cd19534   45 ALVEHHDALRMRFRREDGGWQQRIRGDvEELFRLEVVDLS---SLAQAAAIEALAAEAQSSLDLEEGPLLAAALFDGtDG 121

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308051767  80 AGRLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19534  122 GDRLLLVIHHLVVDGVSWRILLEDLEAAYEQALAG 156

Uncharacterized conserved protein, contains a NRPS condensation (elongation) domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVHKQGQWQQYHSDDWEsFGFEVMDLSPMSSGEQLTTMAE-ISEAQQRSLNLEKGPLISVVFFQLGDA 80
Cdd:COG4908   41 ELVRRHPALRTRFVEEDGEPVQRIDPDAD-LPLEVVDLSALPEPEREAELEElVAEEASRPFDLARGPLLRAALIRLGED 119

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308051767  81 G-RLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:COG4908  120 EhVLLLTIHHIISDGWSLGILLRELAALYAALLEG 154

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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVHKQGQWQQYHSDD-WESFGFEVMDLSpmsSGEQLTTMAEISEAQQRSLNLEKGPLISVVFFQL-GD 79
Cdd:cd19534   45 ALVEHHDALRMRFRREDGGWQQRIRGDvEELFRLEVVDLS---SLAQAAAIEALAAEAQSSLDLEEGPLLAAALFDGtDG 121

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308051767  80 AGRLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19534  122 GDRLLLVIHHLVVDGVSWRILLEDLEAAYEQALAG 156

Uncharacterized conserved protein, contains a NRPS condensation (elongation) domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVHKQGQWQQYHSDDWEsFGFEVMDLSPMSSGEQLTTMAE-ISEAQQRSLNLEKGPLISVVFFQLGDA 80
Cdd:COG4908   41 ELVRRHPALRTRFVEEDGEPVQRIDPDAD-LPLEVVDLSALPEPEREAELEElVAEEASRPFDLARGPLLRAALIRLGED 119

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 308051767  81 G-RLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:COG4908  120 EhVLLLTIHHIISDGWSLGILLRELAALYAALLEG 154

peptide synthase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767    3 LLYHHDALRLRFVHKQGQWQQYHSDdwESFGFEVMDLSPMSSGEQLTtmaEISEAQQRSLNLEKGPLISVVFFQLGDAG- 81
Cdd:PRK12316 3683 LVEHHDALRLRFVEDAGGWTAEHLP--VELGGALLWRAELDDAEELE---RLGEEAQRSLDLADGPLLRALLATLADGSq 3757

                          90       100       110
                  ....*....|....*....|....*....|...
gi 308051767   82 RLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:PRK12316 3758 RLLLVIHHLVVDGVSWRILLEDLQQAYQQLLQG 3790

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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767    2 KLLYHHDALRLRFVHKQGQWQQYHSDDWESFGFEVMDLSPMSSGEQLTTMAEISEAQ-QRSLNLEKGPLISVVFFQLGDA 80
Cdd:pfam00668  50 ELINRHDALRTVFIRQENGEPVQVILEERPFELEIIDISDLSESEEEEAIEAFIQRDlQSPFDLEKGPLFRAGLFRIAEN 129

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 308051767   81 G-RLLIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:pfam00668 130 RhHLLLSMHHIIVDGVSLGILLRDLADLYQQLLKG 164

LCL-type Condensation (C) domain of non-ribosomal peptide synthetases(NRPSs) and similar domains including the C-domain of SgcC5, a free-standing NRPS with both ester- and amide- bond forming activity; LCL-type Condensation (C) domains catalyze peptide bond formation between two L-amino acids, ((L)C(L)). C-domains of NRPSs catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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). In addition to the LCL-type, there are various subtypes of C-domains such as 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 epimerization (E) domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain. Streptomyces globisporus SgcC5 is a free-standing NRPS condensation enzyme (rather than a modular NRPS), which catalyzes the condensation between the SgcC2-tethered (S)-3-chloro-5-hydroxy-beta-tyrosine and (R)-1phenyl-1,2-ethanediol, forming an ester bond, during the synthesis of the chromoprotein enediyne antitumor antibiotic C-1027. It has some acceptor substrate promiscuity as it has been shown to also catalyze the formation of an amide bond between SgcC2-tethered (S)-3-chloro-5-hydroxy-beta-tyrosine and a mimic of the enediyne core acceptor substrate having an amine at its C-2 position. C-domains typically have a conserved HHxxxD motif at the active site; mutations in this motif can abolish or diminish condensation activity. An HHxx[SAG]DGxSx(6)[ED] motif is characteristic of LCL-type C-domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   7 HDALRLRFVHKQGQ-WQQYHSDDweSFGFEVMDLSPMSSGEQLTTMAE-ISEAQQRSLNLEKGPLISVVFFQLGDAG-RL 83
Cdd:cd19531   52 HEALRTTFVEVDGEpVQVILPPL--PLPLPVVDLSGLPEAEREAEAQRlAREEARRPFDLARGPLLRATLLRLGEDEhVL 129

                         90       100       110
                 ....*....|....*....|....*....|.
gi 308051767  84 LIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19531  130 LLTMHHIVSDGWSMGVLLRELAALYAAFLAG 160

Cyc (heterocyclization) domain of nonribosomal peptide synthetases (NRPSs); belongs to the Condensation-domain family; Cyc (heterocyclization) domains catalyze two separate reactions in the creation of heterocyclized peptide products in nonribosomal peptide synthesis: amide bond formation followed by intramolecular cyclodehydration between a Cys, Ser, or Thr side chain and a carbonyl carbon on the peptide backbone to form a thiazoline, oxazoline, or methyloxazoline ring. Cyc-domains are homologous to standard NRPS Condensation (C) domains. C-domains typically have a conserved HHxxxD motif at the active site; Cyc-domains have an alternative, conserved DxxxxD active site motif, mutation of the aspartate residues in this motif can abolish or diminish condensation activity. 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 Cyc-domains. 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 epimerization (E) domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFvHKQGQwQQYHsDDWESFGFEVMDLSPMSSGEQLTTMAEISEAQ-QRSLNLEKGPLISVVFFQL-GD 79
Cdd:cd19535   48 KLIARHPMLRAVF-LDDGT-QQIL-PEVPWYGITVHDLRGLSEEEAEAALEELRERLsHRVLDVERGPLFDIRLSLLpEG 124

                         90       100       110
                 ....*....|....*....|....*....|.
gi 308051767  80 AGRLLIIIHHLVVDGVSWRIFLEDLLTSYHQ 110
Cdd:cd19535  125 RTRLHLSIDLLVADALSLQILLRELAALYED 155

DCL-type Condensation domain of nonribosomal peptide synthetases (NRPSs), which catalyzes the condensation between a D-aminoacyl/peptidyl-PCP donor and a L-aminoacyl-PCP acceptor; The DCL-type Condensation (C) domain catalyzes the condensation between a D-aminoacyl/peptidyl-PCP donor and a L-aminoacyl-PCP acceptor. This domain is D-specific for the peptidyl donor and L-specific for the aminoacyl acceptor ((D)C(L)); this is in contrast with the standard LCL domains which catalyze peptide bond formation between two L-amino acids, and the restriction of ribosomes to use only L-amino acids. C domains of nonribosomal peptide synthetases (NRPSs) catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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 in addition to the LCL- and DCL-types such as 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 epimerization (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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   7 HDALRLRFVHKQ-GQWQQYHSDDWEsFGFEVMDLSPMSSGEQLTTMAEISEA-QQRSLNLEKGPLISVVFFQLGDAG-RL 83
Cdd:cd19543   52 HPILRTSFVWEGlGEPLQVVLKDRK-LPWRELDLSHLSEAEQEAELEALAEEdRERGFDLARAPLMRLTLIRLGDDRyRL 130

                         90       100       110
                 ....*....|....*....|....*....|.
gi 308051767  84 LIIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19543  131 VWSFHHILLDGWSLPILLKELFAIYAALGEG 161

LCL-type Condensation domain of non-ribosomal peptide synthetases (NRPSs) and similar domains; LCL-type Condensation (C) domains catalyze peptide bond formation between two L-amino acids, ((L)C(L)). C-domains of NRPSs catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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). In addition to the LCL-type, there are various subtypes of C-domains such as 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 epimerization (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. An HHxx[SAG]DGxSx(6)[ED] motif is characteristic of LCL-type C-domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   7 HDALRLRFVHKQGQ-WQQYHSDDWESFGFEVMDLSPMSsgeqltTMAEISEAQQRSLNLEKGPLISVVFFQLGDAGR-LL 84
Cdd:cd19538   52 HESLRTVFPEEDGVpYQLILEEDEATPKLEIKEVDEEE------LESEINEAVRYPFDLSEEPPFRATLFELGENEHvLL 125

                         90       100       110
                 ....*....|....*....|....*....|
gi 308051767  85 IIIHHLVVDGVSWRIFLEDLLTSYHQLETG 114
Cdd:cd19538  126 LLLHHIAADGWSLAPLTRDLSKAYRARCKG 155

Condensation domain of hybrid polyketide synthetase/nonribosomal peptide synthetases (PKS/NRPSs), similar to Bacillus subtilis PksJ; Condensation (C) domains of nonribosomal peptide synthetases (NRPSs) catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. Hybrid PKS/NRPS create polymers containing both polyketide and amide linkages. C-domains typically have a conserved HHxxxD motif at the active site; mutations in this motif can abolish or diminish condensation activity. Members of this subfamily have the typical C-domain HHxxxD motif. PksJ is involved in some intermediate steps for the synthesis of the antibiotic polyketide bacillaene which is important in secondary metabolism. 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 epimerization (E) domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767  30 ESFGFEVMDLSPMSSGEqltTMAEISEAQQRSLNLEKGPLISVVFFQLGDAGR-LLIIIHHLVVDGVSWRIFLEDLLTSY 108
Cdd:cd20484   74 KPLSFQEEDISSLKESE---IIAYLREKAKEPFVLENGPLMRVHLFSRSEQEHfVLITIHHIIFDGSSSLTLIHSLLDAY 150

                 ....*.
gi 308051767 109 HQLETG 114
Cdd:cd20484  151 QALLQG 156

Condensation domain of hybrid polyketide synthetase/nonribosomal peptide synthetases (PKS/NRPSs); Condensation (C) domains of nonribosomal peptide synthetases (NRPSs) catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. Hybrid PKS/NRPS create polymers containing both polyketide and amide linkages. C-domains typically have a conserved HHxxxD motif at the active site; mutations in this motif can abolish or diminish condensation activity. Most members of this subfamily have the typical C-domain HHXXXD motif. 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 epimerization (E) domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   7 HDALRLRFVHKQGQWQQYHSDDwESFGFEVMDLSPMSSGEQLTTmAEISEAQQRSLNLEKGPLISVVFFQLGDAG-RLLI 85
Cdd:cd20483   52 HEVLRTAYFEGDDFGEQQVLDD-PSFHLIVIDLSEAADPEAALD-QLVRNLRRQELDIEEGEVIRGWLVKLPDEEfALVL 129

                         90       100
                 ....*....|....*....|...
gi 308051767  86 IIHHLVVDGVSWRIFLEDLLTSY 108
Cdd:cd20483  130 ASHHIAWDRGSSKSIFEQFTALY 152

DCL-type Condensation domains of nonribosomal peptide synthetases (NRPSs), such as terminal fungal CT domains and Dual Epimerization/Condensation (E/C) domains; Condensation (C) domains of nonribosomal peptide synthetases (NRPSs) catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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 [D-specific for the peptidyl donor and L-specific for the aminoacyl acceptor ((D)C(L))], 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 epimerization (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        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   7 HDALRLRFVHKQG----QWQQYHSDdwesFGFEVMDLSPMSsgEQLTTMAE-ISEAQQRSLNLEKGPLISVVFFQLGDAG 81
Cdd:cd19536   52 HDILRTSFIEDGLgqpvQVVHRQAQ----VPVTELDLTPLE--EQLDPLRAyKEETKIRRFDLGRAPLVRAALVRKDERE 125

                         90       100       110
                 ....*....|....*....|....*....|..
gi 308051767  82 R--LLIIIHHLVVDGVSWRIFLEDLLTSYHQL 111
Cdd:cd19536  126 RflLVISDHHSILDGWSLYLLVKEILAVYNQL 157

Terminal Condensation (CT)-like domains of nonribosomal peptide synthetases (NRPSs); Unlike bacterial NRPS, which typically have specialized terminal thioesterase (TE) domains to cyclize peptide products, many fungal NRPSs employ a terminal condensation-like (CT) domain to produce macrocyclic peptidyl products (e.g. cyclosporine and echinocandin). Domains in this subfamily (which includes both terminal and non-terminal domains) typically have a non-canonical conserved [SN]HxxxDx(14)Y motif at their active site compared to the standard Condensation (C) domain active site motif (HHxxxD). C-domains of NRPSs catalyze peptide bond formation within (usually) large multi-modular enzymatic complexes. 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 epimerization (E) domain, the ester-bond forming C-domain, dual E/C (epimerization and condensation) domains, and the X-domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767   2 KLLYHHDALRLRFVH--KQGQWQQ--YHSDDWESFGFEVMDlspmssgEQLTTMAEISEAQQRslnLEKGPLISVVFFQL 77
Cdd:cd19542   45 QLVQRHDILRTVFVEssAEGTFLQvvLKSLDPPIEEVETDE-------DSLDALTRDLLDDPT---LFGQPPHRLTLLET 114

                         90       100       110
                 ....*....|....*....|....*....|....
gi 308051767  78 GDAG-RLLIIIHHLVVDGVSWRIFLEDLLTSYHQ 110
Cdd:cd19542  115 SSGEvYLVLRISHALYDGVSLPIILRDLAAAYNG 148

peptide synthase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 308051767    3 LLYHHDALRLRFVHKQG-QWQQYHSD-----DWESFGfevmDLSPMSSGEQLTTMAEiSEAQQrSLNLEKGPLISVVFFQ 76
Cdd:PRK05691 1775 LILRHETLRTTFPSVDGvPVQQVAEDsglrmDWQDFS----ALPADARQQRLQQLAD-SEAHQ-PFDLERGPLLRACLVK 1848

                          90       100
                  ....*....|....*....|....*....
gi 308051767   77 LGDAGRLLII-IHHLVVDGVSWRIFLEDL 104
Cdd:PRK05691 1849 AAEREHYFVLtLHHIVTEGWAMDIFAREL 1877