peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAG-QVLLLDQP 79
Cdd:PRK12467  1620 GVGPEVLVGIAVERSLEMVVGLLAILKAGGAYVPLDPEYPRERLAYMIEDSGIELLLTQSHLQARLPLPDGlRSLVLDQE 1699

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2648899396   80 GE-LGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12467  1700 DDwLEGYSDSNPAVNLAPQNLAYVIYTSGSTGRP 1733

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAG-QVLLLDQP 79
Cdd:PRK12467  1620 GVGPEVLVGIAVERSLEMVVGLLAILKAGGAYVPLDPEYPRERLAYMIEDSGIELLLTQSHLQARLPLPDGlRSLVLDQE 1699

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2648899396   80 GE-LGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12467  1700 DDwLEGYSDSNPAVNLAPQNLAYVIYTSGSTGRP 1733

bacitracin synthetase and related proteins; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes bacitracin synthetases 1, 2, and 3 (BA1, also known as ATP-dependent cysteine adenylase or cysteine activase, BA2, also known as ATP-dependent lysine adenylase or lysine activase, and BA3, also known as ATP-dependent isoleucine adenylase or isoleucine activase) in Bacilli. Bacitracin is a mixture of related cyclic peptides used as a polypeptide antibiotic. This family also includes gramicidin synthetase 1 involved in synthesis of the cyclic peptide antibiotic gramicidin S via activation of phenylalanine. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLpAFAGQVLLL-DQP 79
Cdd:cd17655    43 GVGPDTIVGIMAERSLEMIVGILGILKAGGAYLPIDPDYPEERIQYILEDSGADILLTQSHLQPPI-AFIGLIDLLdEDT 121

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2648899396  80 GELGGYSQQVPACRlhPENLAYVIYTSGSTGRP 112
Cdd:cd17655   122 IYHEESENLEPVSK--SDDLAYVIYTSGSTGKP 152

AMP-binding enzyme;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLR-------EQLPAFAGQV 73
Cdd:pfam00501  42 GVGKGDRVAILLPNSPEWVVAFLACLKAGAVYVPLNPRLPAEELAYILEDSGAKVLITDDALKleelleaLGKLEVVKLV 121

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2648899396  74 LLLDQPGELGG----------YSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:pfam00501 122 LVLDRDPVLKEeplpeeakpaDVPPPPPPPPDPDDLAYIIYTSGTTGKP 170

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAG-QVLLLDQP 79
Cdd:PRK12467  1620 GVGPEVLVGIAVERSLEMVVGLLAILKAGGAYVPLDPEYPRERLAYMIEDSGIELLLTQSHLQARLPLPDGlRSLVLDQE 1699

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2648899396   80 GE-LGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12467  1700 DDwLEGYSDSNPAVNLAPQNLAYVIYTSGSTGRP 1733

EntF, seryl-AMP synthase component of non-ribosomal peptide synthetase [Secondary metabolites biosynthesis, transport and catabolism];

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAGQVLLLDQPg 80
Cdd:COG1020    522 GVGPGDLVGVCLERSLEMVVALLAVLKAGAAYVPLDPAYPAERLAYMLEDAGARLVLTQSALAARLPELGVPVLALDAL- 600

                           90       100       110
                   ....*....|....*....|....*....|..
gi 2648899396   81 ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:COG1020    601 ALAAEPATNPPVPVTPDDLAYVIYTSGSTGRP 632

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAG-QVLLLDQP 79
Cdd:PRK12316   557 GVGPDVLVGVAMERSIEMVVALLAILKAGGAYVPLDPEYPAERLAYMLEDSGVQLLLSQSHLGRKLPLAAGvQVLDLDRP 636

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2648899396   80 G-ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12316   637 AaWLEGYSEENPGTELNPENLAYVIYTSGSTGKP 670

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAG-QVLLLDQP 79
Cdd:PRK12467   558 GVGPDVLVGIAVERSIEMVVGLLAVLKAGGAYVPLDPEYPQDRLAYMLDDSGVRLLLTQSHLLAQLPVPAGlRSLCLDEP 637

                           90       100       110
                   ....*....|....*....|....*....|....
gi 2648899396   80 G-ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12467   638 AdLLCGYSGHNPEVALDPDNLAYVIYTSGSTGQP 671

bacitracin synthetase and related proteins; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes bacitracin synthetases 1, 2, and 3 (BA1, also known as ATP-dependent cysteine adenylase or cysteine activase, BA2, also known as ATP-dependent lysine adenylase or lysine activase, and BA3, also known as ATP-dependent isoleucine adenylase or isoleucine activase) in Bacilli. Bacitracin is a mixture of related cyclic peptides used as a polypeptide antibiotic. This family also includes gramicidin synthetase 1 involved in synthesis of the cyclic peptide antibiotic gramicidin S via activation of phenylalanine. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLpAFAGQVLLL-DQP 79
Cdd:cd17655    43 GVGPDTIVGIMAERSLEMIVGILGILKAGGAYLPIDPDYPEERIQYILEDSGADILLTQSHLQPPI-AFIGLIDLLdEDT 121

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2648899396  80 GELGGYSQQVPACRlhPENLAYVIYTSGSTGRP 112
Cdd:cd17655   122 IYHEESENLEPVSK--SDDLAYVIYTSGSTGKP 152

The adenylation domain of nonribosomal peptide synthetases (NRPS), including Bacillus subtilis termination module Surfactin (SrfA-C); The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and, in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions. This family includes the adenylation domain of the Bacillus subtilis termination module (Surfactin domain, SrfA-C) which recognizes a specific amino acid building block, which is then activated and transferred to the terminal thiol of the 4'-phosphopantetheine (Ppan) arm of the downstream peptidyl carrier protein (PCP) domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLpafAGQVLLLDQPG 80
Cdd:cd12117    43 GVGPGDVVGVLAERSPELVVALLAVLKAGAAYVPLDPELPAERLAFMLADAGAKVLLTDRSLAGRA---GGLEVAVVIDE 119

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:cd12117   120 ALDAGPAGNPAVPVSPDDLAYVMYTSGSTGRP 151

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396    1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLReqLPAFAG-QVLLLDQP 79
Cdd:PRK12316  3103 GVGPDVLVGVAVERSLEMVVGLLAILKAGGAYVPLDPEYPEERLAYMLEDSGAQLLLSQSHLR--LPLAQGvQVLDLDRG 3180

                           90       100       110
                   ....*....|....*....|....*....|...
gi 2648899396   80 GElgGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK12316  3181 DE--NYAEANPAIRTMPENLAYVIYTSGSTGKP 3211

Peptide Synthetase; The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester bond to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAGQVLLldQPG 80
Cdd:cd17646    44 GVGPEDRVAVLLPRSADLVVALLAVLKAGAAYLPLDPGYPADRLAYMLADAGPAVVLTTADLAARLPAGGDVALL--GDE 121

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:cd17646   122 ALAAPPATPPLVPPRPDNLAYVIYTSGSTGRP 153

non-ribosomal peptide synthetase; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes pyoverdine biosynthesis protein PvdJ involved in the synthesis of pyoverdine, which consists of a chromophore group attached to a variable peptide chain and comprises around 6-12 amino acids that are specific for each Pseudomonas species, and for which the peptide might be first synthesized before the chromophore assembly. Also included is ornibactin biosynthesis protein OrbI; ornibactin is a tetrapeptide siderophore with an l-ornithine-d-hydroxyaspartate-l-serine-l-ornithine backbone. The adenylation domain at the N-terminal of OrbI possibly initiates the ornibactin with the binding of N5-hydroxyornithine. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd17649    33 GVGPEVRVGIALERSLEMVVALLAILKAGGAYVPLDPEYPAERLRYMLEDSGAGLLLTH--------------------- 91

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlHPENLAYVIYTSGSTGRP 112
Cdd:cd17649    92 --------------HPRQLAYVIYTSGSTGTP 109

The adenylation domain of nonribosomal peptide synthetases (NRPS), including salinosporamide A polyketide synthase; The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions. This family includes the myxovirescin (TA) antibiotic biosynthetic gene in Myxococcus xanthus; TA production plays a role in predation. It also includes the salinosporamide A polyketide synthase which is involved in the biosynthesis of salinosporamide A, a marine microbial metabolite whose chlorine atom is crucial for potent proteasome inhibition and anticancer activity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAGQVLLLDQPG 80
Cdd:cd12116    33 GVGPGDRVAVYLPRSARLVAAMLAVLKAGAAYVPLDPDYPADRLRYILEDAEPALVLTDDALPDRLPAGLPVLLLALAAA 112

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 ELGGYSQQVPAcrlHPENLAYVIYTSGSTGRP 112
Cdd:cd12116   113 AAAPAAPRTPV---SPDDLAYVIYTSGSTGRP 141

similar to adenylation domain of cytotrienin synthetase CytC1; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes Streptomyces sp. cytotrienin synthetase (CytC1), a relatively promiscuous adenylation enzyme that installs the aminoacyl moieties on the phosphopantetheinyl arm of the holo carrier protein CytC2. Also included are Streptomyces sp Thr1, involved in the biosynthesis of 4-chlorothreonine, Pseudomonas aeruginosa pyoverdine synthetase D (PvdD), involved in the biosynthesis of the siderophore pyoverdine and Pseudomonas syringae syringopeptin synthetase, where syringpeptin is a necrosis-inducing phytotoxin that functions as a virulence determinant in the plant-pathogen interaction. The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester bond to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd17643    33 GVGPGDRVALALPRSAELIVALLAILKAGGAYVPIDPAYPVERIAFILADSGPSLLLTD--------------------- 91

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd17643    92 ---------------PDDLAYVIYTSGSTGRP 108

similar to adenylation domain of plipastatin synthase (PpsD); This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes bacitracin synthetase 1 (BacA) in Bacillus licheniformis, tyrocidine synthetase in Brevibacillus brevis, plipastatin synthase (PpsD, an important antifungal protein) in Bacillus subtilis and mannopeptimycin peptide synthetase (MppB) in Streptomyces hygroscopicus. Plipastatin has strong fungitoxic activity and is involved in inhibition of phospholipase A2 and biofilm formation. Bacitracin, a mixture of related cyclic peptides, is used as a polypeptide antibiotic while function of tyrocidine is thought to be regulation of sporulation. MppB is involved in biosynthetic pathway of mannopeptimycin, a novel class of mannosylated lipoglycopeptides. The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester bond to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd17650    33 GVAPGSVVGVCADRSLDAIVGLLAVLKAGGAYVPIDPDYPAERLQYMLEDSGAKLLLTQ--------------------- 91

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd17650    92 ---------------PEDLAYVIYTSGTTGKP 108

The adenylation domain of nonribosomal peptide synthetases (NRPS), including Saframycin A gene cluster from Streptomyces lavendulae; The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions. This family includes the saframycin A gene cluster from Streptomyces lavendulae which implicates the NRPS system for assembling the unusual tetrapeptidyl skeleton in an iterative manner. It also includes saframycin Mx1 produced by Myxococcus xanthus NRPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd12115    45 GVGPESRVGVCLERTPDLVVALLAVLKAGAAYVPLDPAYPPERLRFILEDAQARLVLTD--------------------- 103

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd12115   104 ---------------PDDLAYVIYTSGSTGRP 120

The adenylation (A) domain of siderophore-synthesizing nonribosomal peptide synthetases (NRPS); The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. This family of siderophore-synthesizing NRPS includes the third adenylation domain of SidN from the endophytic fungus Neotyphodium lolii, ferrichrome siderophore synthetase, HC-toxin synthetase, and enniatin synthase. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTqahlreqlpafagqvllldqpg 80
Cdd:cd05918    45 GVGPGVFVPLCFEKSKWAVVAMLAVLKAGGAFVPLDPSHPLQRLQEILQDTGAKVVLT---------------------- 102

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrLHPENLAYVIYTSGSTGRP 112
Cdd:cd05918   103 -------------SSPSDAAYVIFTSGSTGKP 121

adenylation (A) domain of linear gramicidin synthetase (LgrA) and similar proteins; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes linear gramicidin synthetase (LgrA) in Brevibacillus brevis. LgrA has a formylation domain fused to the N-terminal end that formylates its substrate for linear gramicidin synthesis to proceed. This formyl group is essential for the clinically important antibacterial activity of gramicidin by enabling head-to-head gramicidin dimers to make a beta-helical pore in gram-positive bacterial membranes, allowing free passage of monovalent cations, destroying the ion gradient and killing bacteria. This family also includes bacitracin synthetase 1 (known as ATP-dependent cysteine adenylase or BA1); it activates cysteine, incorporates two D-amino acids, releases and cyclizes the mature bacitracin, an antibiotic that is a mixture of related cyclic peptides that disrupt gram positive bacteria by interfering with cell wall and peptidoglycan synthesis. Also included is surfactin synthetase which activates and polymerizes the amino acids Leu, Glu, Asp, and Val to form the antibiotic surfactin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd17645    44 GVKPDDQVGIMLDKSLDMIAAILGVLKAGGAYVPIDPDYPGERIAYMLADSSAKILLTN--------------------- 102

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd17645   103 ---------------PDDLAYVIYTSGSTGLP 119

N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase; This family contains ACV synthetase (ACVS, EC 6.3.2.26; also known as N-(5-amino-5-carboxypentanoyl)-L-cysteinyl-D-valine synthase or delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase) is involved in medically important antibiotic biosynthesis. ACV synthetase is active in an early step in the penicillin G biosynthesis pathway which involves the formation of the tripeptide 6-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV); each of the constituent amino acids of the tripeptide ACV are activated as aminoacyl-adenylates with peptide bonds formed through the participation of amino acid thioester intermediates. ACV is then cyclized by the action of isopenicillin N synthase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   4 PESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpgelg 83
Cdd:cd17648    37 PDDLVGLVLDKSELMIIAILAVWKAGAAYVPIDPSYPDERIQFILEDTGARVVITN------------------------ 92

                          90       100
                  ....*....|....*....|....*....
gi 2648899396  84 gysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd17648    93 ------------STDLAYAIYTSGTTGKP 109

O-succinylbenzoic acid-CoA ligase MenE or related acyl-CoA synthetase (AMP-forming) [Lipid transport and metabolism]; O-succinylbenzoic acid-CoA ligase MenE or related acyl-CoA synthetase (AMP-forming) is part of the Pathway/BioSystem: Menaquinone biosynthesis

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTqahlreqlpafagqvllldqpg 80
Cdd:COG0318    45 GVGPGDRVALLLPNSPEFVVAFLAALRAGAVVVPLNPRLTAEELAYILEDSGARALVT---------------------- 102

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhpenlAYVIYTSGSTGRP 112
Cdd:COG0318   103 -------------------ALILYTSGTTGRP 115

D-alanine:D-alanyl carrier protein ligase (DltA) and similar proteins; This family includes D-alanyl carrier protein ligase DltA and aliphatic beta-amino acid adenylation enzymes IdnL1 and CmiS6. DltA incorporates D-ala in techoic acids in gram-positive bacteria via a two-step process, starting with adenylation of D-alanine that transfers D-alanine to the D-alanyl carrier protein. IdnL1, a short-chain aliphatic beta-amino acid adenylation enzyme, recognizes 3-aminobutanoic acid, and is involved in the synthesis of the macrolactam antibiotic incednine. CmiS6 is a medium-chain beta-amino acid adenylation enzyme that recognizes 3-aminononanoic acid, and is involved in the synthesis of cremimycin, also a macrolactam antibiotic. The adenylation (A) domain of NRPS recognizes a specific amino acid or hydroxy acid and activates it as an (amino) acyl adenylate by hydrolysis of ATP. The activated acyl moiety then forms a thioester bond to the enzyme-bound cofactor phosphopantetheine of a peptidyl carrier protein domain. NRPSs are large multifunctional enzymes which synthesize many therapeutically useful peptides in bacteria and fungi via a template-directed, nucleic acid independent nonribosomal mechanism. These natural products include antibiotics, immunosuppressants, plant and animal toxins, and enzyme inhibitors. NRPS has a distinct modular structure in which each module is responsible for the recognition, activation, and in some cases, modification of a single amino acid residue of the final peptide product. The modules can be subdivided into domains that catalyze specific biochemical reactions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQahlreqlpafagqvllldqpg 80
Cdd:cd05945    37 GLDAGDPVVVYGHKSPDAIAAFLAALKAGHAYVPLDASSPAERIREILDAAKPALLIAD--------------------- 95

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacrlhPENLAYVIYTSGSTGRP 112
Cdd:cd05945    96 ---------------GDDNAYIIFTSGSTGRP 112

long-chain-fatty-acid--CoA ligase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHL-------REQLPAFAGQV 73
Cdd:PRK07656   51 GIGKGDRVAIWAPNSPHWVIAALGALKAGAVVVPLNTRYTADEAAYILARGDAKALFVLGLFlgvdysaTTRLPALEHVV 130

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2648899396  74 LLLDQPGE------------LGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK07656  131 ICETEEDDphtekmktftdfLAAGDPAERAPEVDPDDVADILFTSGTTGRP 181

Acyl-coenzyme A synthetase/AMP-(fatty) acid ligase [Lipid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHL----------------RE 64
Cdd:COG0365    60 GVKKGDRVAIYLPNIPEAVIAMLACARIGAVHSPVFPGFGAEALADRIEDAEAKVLITADGGlrggkvidlkekvdeaLE 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2648899396  65 QLPAFAgQVLLLDQPG-------------ELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:COG0365   140 ELPSLE-HVIVVGRTGadvpmegdldwdeLLAAASAEFEPEPTDADDPLFILYTSGTTGKP 199

Firefly luciferase of light emitting insects and 4-Coumarate-CoA Ligase (4CL); This family contains insect firefly luciferases that share significant sequence similarity to plant 4-coumarate:coenzyme A ligases, despite their functional diversity. Luciferase catalyzes the production of light in the presence of MgATP, molecular oxygen, and luciferin. In the first step, luciferin is activated by acylation of its carboxylate group with ATP, resulting in an enzyme-bound luciferyl adenylate. In the second step, luciferyl adenylate reacts with molecular oxygen, producing an enzyme-bound excited state product (Luc=O*) and releasing AMP. This excited-state product then decays to the ground state (Luc=O), emitting a quantum of visible light.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQL-------------- 66
Cdd:cd05911    31 GLKKGDVVGIISPNSTYYPPVFLGCLFAGGIFSAANPIYTADELAHQLKISKPKVIFTDPDGLEKVkeaakelgpkdkii 110

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2648899396  67 -----PAFAGQVLLLDQPGELGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:cd05911   111 vlddkPDGVLSIEDLLSPTLGEEDEDLPPPLKDGKDDTAAILYSSGTTGLP 161

Subfamily of fatty acid CoA ligase (FACL) similar to Fum10p of Gibberella moniliformis; FACL catalyzes the formation of fatty acyl-CoA in a two-step reaction: the formation of a fatty acyl-AMP molecule as an intermediate, followed by the formation of a fatty acyl-CoA. This is a required step before free fatty acids can participate in most catabolic and anabolic reactions. Fum10p is a fatty acid CoA ligase involved in the synthesis of fumonisin, a polyketide mycotoxin, in Gibberella moniliformis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQ---------AHLREQLPAF-- 69
Cdd:cd05926    35 GIKKGDRVAIALPNGLEFVVAFLAAARAGAVVAPLNPAYKKAEFEFYLADLGSKLVLTPkgelgpasrAASKLGLAILel 114

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2648899396  70 ---AGQVLLLDQPGELGG--------YSQQVPacrlHPENLAYVIYTSGSTGRP 112
Cdd:cd05926   115 aldVGVLIRAPSAESLSNlladkknaKSEGVP----LPDDLALILHTSGTTGRP 164

4-Coumarate-CoA Ligase (4CL); 4-Coumarate:coenzyme A ligase is a key enzyme in the phenylpropanoid metabolic pathway for monolignol and flavonoid biosynthesis. It catalyzes the synthesis of hydroxycinnamate-CoA thioesters in a two-step reaction, involving the formation of hydroxycinnamate-AMP anhydride and the nucleophilic substitution of AMP by CoA. The phenylpropanoid pathway is one of the most important secondary metabolism pathways in plants and hydroxycinnamate-CoA thioesters are the precursors of lignin and other important phenylpropanoids.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQLPAFAGQVLLLDQPG 80
Cdd:cd05904    53 GGRKGDVVLLLSPNSIEFPVAFLAVLSLGAVVTTANPLSTPAEIAKQVKDSGAKLAFTTAELAEKLASLALPVVLLDSAE 132

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2648899396  81 ELGGYSQ---------QVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:cd05904   133 FDSLSFSdllfeadeaEPPVVVIKQDDVAALLYSSGTTGRS 173

malonyl-CoA synthase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREQL-----PAFAGQVLL 75
Cdd:PRK07514   49 GVKPGDRVAVQVEKSPEALALYLATLRAGAVFLPLNTAYTLAELDYFIGDAEPALVVCDPANFAWLskiaaAAGAPHVET 128

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2648899396  76 LDQPGE------LGGYSQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK07514  129 LDADGTgslleaAAAAPDDFETVPRGADDLAAILYTSGTTGRS 171

Uncharacterized subfamily of Acetyl-CoA synthetase like family (ACS); This family is most similar to acetyl-CoA synthetase. Acetyl-CoA synthetase (ACS) catalyzes the formation of acetyl-CoA from acetate, CoA, and ATP. Synthesis of acetyl-CoA is carried out in a two-step reaction. In the first step, the enzyme catalyzes the synthesis of acetyl-AMP intermediate from acetate and ATP. In the second step, acetyl-AMP reacts with CoA to produce acetyl-CoA. This enzyme is only present in bacteria.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLREqlpafagqvllldqpg 80
Cdd:cd05969    21 GVGKGDRVFVLSPRSPELYFSMLGIGKIGAVICPLFSAFGPEAIRDRLENSEAKVLITTEELYE---------------- 84

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2648899396  81 elggysqqvpacRLHPENLAYVIYTSGSTGRP 112
Cdd:cd05969    85 ------------RTDPEDPTLLHYTSGTTGTP 104

o-succinylbenzoate--CoA ligase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   1 GVGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQ---AHLREQLPAFAG--QVLL 75
Cdd:PRK06839   49 NVKKGERIAILSQNSLEYIVLLFAIAKVECIAVPLNIRLTENELIFQLKDSGTTVLFVEktfQNMALSMQKVSYvqRVIS 128

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2648899396  76 LDQPGELggySQQVPACRLHP-ENLAYVI-YTSGSTGRP 112
Cdd:PRK06839  129 ITSLKEI---EDRKIDNFVEKnESASFIIcYTSGTTGKP 164

acyl-CoA synthetase; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   2 VGPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTqahlreqlPAFAGQVLLLDQPGE 81
Cdd:PRK07787   42 VAGARRVAVLATPTLATVLAVVGALIAGVPVVPVPPDSGVAERRHILADSGAQAWLG--------PAPDDPAGLPHVPVR 113

                          90       100       110
                  ....*....|....*....|....*....|.
gi 2648899396  82 LGGYSQQVPAcRLHPENLAYVIYTSGSTGRP 112
Cdd:PRK07787  114 LHARSWHRYP-EPDPDAPALIVYTSGTTGPP 143

Eukaryotic long-chain fatty acid CoA synthetase (LC-FACS); The members of this family are eukaryotic fatty acid CoA synthetases that activate fatty acids with chain lengths of 12 to 20. LC-FACS catalyzes the formation of fatty acyl-CoA in a two-step reaction: the formation of a fatty acyl-AMP molecule as an intermediate, and the formation of a fatty acyl-CoA. This is a required step before free fatty acids can participate in most catabolic and anabolic reactions. Organisms tend to have multiple isoforms of LC-FACS genes with multiple splice variants. For example, nine genes are found in Arabidopsis and six genes are expressed in mammalian cells.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2648899396   3 GPESLVGIAAERSLEMVVGLLAILKAGAAYVPLDPDYPAERLAYMFEDSGIELLLTQAHLReqlpafagqVLLLDQPGEL 82
Cdd:cd05927    30 APASFVGIYSINRPEWIISELACYAYSLVTVPLYDTLGPEAIEYILNHAEISIVFCDAGVK---------VYSLEEFEKL 100

                          90       100       110
                  ....*....|....*....|....*....|
gi 2648899396  83 GGySQQVPACRLHPENLAYVIYTSGSTGRP 112
Cdd:cd05927   101 GK-KNKVPPPPPKPEDLATICYTSGTTGNP 129