Adenylate forming domain, Class I superfamily; This family includes acyl- and aryl-CoA ligases, as well as the adenylation domain of nonribosomal peptide synthetases and firefly luciferases. The adenylate-forming enzymes catalyze an ATP-dependent two-step reaction to first activate a carboxylate substrate as an adenylate and then transfer the carboxylate to the pantetheine group of either coenzyme A or an acyl-carrier protein. The active site of the domain is located at the interface of a large N-terminal subdomain and a smaller C-terminal subdomain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd05930    1 PDAVAVVDGDQSLTYAELDARANRLARYLRERGVGPGDLVAVLLERSLEMVVAILAVLKAGAAYVPLDPSYPAERLAYIL 80

                         90
                 ....*....|....*.
gi 489340094  82 KDSGASLLLTQPGCSA 97
Cdd:cd05930   81 EDSGAKLVLTDPDDLA 96

The adenylation domain of 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 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 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd05930    1 PDAVAVVDGDQSLTYAELDARANRLARYLRERGVGPGDLVAVLLERSLEMVVAILAVLKAGAAYVPLDPSYPAERLAYIL 80

                         90
                 ....*....|....*.
gi 489340094  82 KDSGASLLLTQPGCSA 97
Cdd:cd05930   81 EDSGAKLVLTDPDDLA 96

peptide synthase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK12316 4564 TPDAVAVVFDEEKLTYAELNRRANRLAHALIARGVGPEVLVGIAMERSAEMMVGLLAVLKAGGAYVPLDPEYPRERLAYM 4643

                          90
                  ....*....|..
gi 489340094   81 LKDSGASLLLTQ 92
Cdd:PRK12316 4644 MEDSGAALLLTQ 4655

AMP-binding enzyme;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGG-SLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSY 79
Cdd:pfam00501   8 TPDKTALEVGEGrRLTYRELDERANRLAAGLRALGVGKGDRVAILLPNSPEWVVAFLACLKAGAVYVPLNPRLPAEELAY 87

                          90       100
                  ....*....|....*....|
gi 489340094   80 MLKDSGASLLLTQPGCSAPN 99
Cdd:pfam00501  88 ILEDSGAKVLITDDALKLEE 107

The adenylation domain of 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 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 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd05930    1 PDAVAVVDGDQSLTYAELDARANRLARYLRERGVGPGDLVAVLLERSLEMVVAILAVLKAGAAYVPLDPSYPAERLAYIL 80

                         90
                 ....*....|....*.
gi 489340094  82 KDSGASLLLTQPGCSA 97
Cdd:cd05930   81 EDSGAKLVLTDPDDLA 96

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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd12117   10 TPDAVAVVYGDRSLTYAELNERANRLARRLRAAGVGPGDVVGVLAERSPELVVALLAVLKAGAAYVPLDPELPAERLAFM 89

                         90
                 ....*....|....
gi 489340094  81 LKDSGASLLLTQPG 94
Cdd:cd12117   90 LADAGAKVLLTDRS 103

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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17646   11 TPDAPAVVDEGRTLTYRELDERANRLAHLLRARGVGPEDRVAVLLPRSADLVVALLAVLKAGAAYLPLDPGYPADRLAYM 90

                         90
                 ....*....|....*...
gi 489340094  81 LKDSGASLLLTQPGCSAP 98
Cdd:cd17646   91 LADAGPAVVLTTADLAAR 108

similar to adenylation domain of virginiamycin S synthetase; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes virginiamycin S synthetase (VisG) in Streptomyces virginiae; VisG is involved in virginiamycin S (VS) biosynthesis as the provider of an L-pheGly molecule, a highly specific substrate for the last condensation step by VisF. This family also includes linear gramicidin synthetase B (LgrB) in Brevibacillus brevis. Substrate specificity analysis using residues of the substrate-binding pockets of all 16 adenylation domains has shown good agreement of the substrate amino acids predicted with the sequence of linear gramicidin. 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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17651    8 TPDAPALVAEGRRLTYAELDRRANRLAHRLRARGVGPGDLVALCARRSAELVVALLAILKAGAAYVPLDPAYPAERLAFM 87

                         90
                 ....*....|....
gi 489340094  81 LKDSGASLLLTQPG 94
Cdd:cd17651   88 LADAGPVLVLTHPA 101

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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd12115   12 TPDAIALVCGDESLTYAELNRRANRLAARLRAAGVGPESRVGVCLERTPDLVVALLAVLKAGAAYVPLDPAYPPERLRFI 91

                         90
                 ....*....|...
gi 489340094  81 LKDSGASLLLTQP 93
Cdd:cd12115   92 LEDAQARLVLTDP 104

peptide synthase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK12316 4564 TPDAVAVVFDEEKLTYAELNRRANRLAHALIARGVGPEVLVGIAMERSAEMMVGLLAVLKAGGAYVPLDPEYPRERLAYM 4643

                          90
                  ....*....|..
gi 489340094   81 LKDSGASLLLTQ 92
Cdd:PRK12316 4644 MEDSGAALLLTQ 4655

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 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd17649    1 PDAVALVFGDQSLSYAELDARANRLAHRLRALGVGPEVRVGIALERSLEMVVALLAILKAGGAYVPLDPEYPAERLRYML 80

                         90
                 ....*....|...
gi 489340094  82 KDSGASLLLTQPG 94
Cdd:cd17649   81 EDSGAGLLLTHHP 93

peptide synthase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK12467 1587 TPEAVALVFGEQELTYGELNRRANRLAHRLIALGVGPEVLVGIAVERSLEMVVGLLAILKAGGAYVPLDPEYPRERLAYM 1666

                          90
                  ....*....|..
gi 489340094   81 LKDSGASLLLTQ 92
Cdd:PRK12467 1667 IEDSGIELLLTQ 1678

similar to adenylation domain of anabaenopeptin synthetase (ApnA); This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes Planktothrix agardhii anabaenopeptin synthetase (ApnA A1), which is capable of activating two chemically distinct amino acids (Arg and Tyr). Structural studies show that the architecture of the active site forces Arg to adopt a Tyr-like conformation, thus explaining the bispecificity. 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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17644   13 TPDAVAVVFEDQQLTYEELNTKANQLAHYLQSLGVKSESLVGICVERSLEMIIGLLAILKAGGAYVPLDPNYPQERLTYI 92

                         90
                 ....*....|...
gi 489340094  81 LKDSGASLLLTQP 93
Cdd:cd17644   93 LEDAQISVLLTQP 105

amino acid adenylation domain; This model represents a domain responsible for the specific recognition of amino acids and activation as adenylyl amino acids. The reaction catalyzed is aa + ATP -> aa-AMP + PPi. These domains are usually found as components of multi-domain non-ribosomal peptide synthetases and are usually called "A-domains" in that context. A-domains are almost invariably followed by "T-domains" (thiolation domains, pfam00550) to which the amino acid adenylate is transferred as a thiol-ester to a bound pantetheine cofactor with the release of AMP (these are also called peptide carrier proteins, or PCPs. When the A-domain does not represent the first module (corresponding to the first amino acid in the product molecule) it is usually preceded by a "C-domain" (condensation domain, pfam00668) which catalyzes the ligation of two amino acid thiol-esters from neighboring modules. This domain is a subset of the AMP-binding domain found in Pfam (pfam00501) which also hits substrate--CoA ligases and luciferases. Sequences scoring in between trusted and noise for this model may be ambiguous as to whether they activate amino acids or other molecules lacking an alpha amino group.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   15 TYAELDMYASRLAAHL-AARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYMLKDSGASLLLTQP 93
Cdd:TIGR01733   1 TYRELDERANRLARHLrAAGGVGPGDRVAVLLERSAELVVAILAVLKAGAAYVPLDPAYPAERLAFILEDAGARLLLTDS 80

                          90
                  ....*....|....
gi 489340094   94 GcSAPNFSGETLEV 107
Cdd:TIGR01733  81 A-LASRLAGLVLPV 93

gramicidin S synthase 2, also known as ATP-dependent proline adenylase; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) contains gramicidin S synthase 2 (also known as ATP-dependent proline adenylase or proline activase or ProA). ProA is a multifunctional enzyme involved in synthesis of the cyclic peptide antibiotic gramicidin S and able to activate and polymerize the amino acids proline, valine, ornithine and leucine. 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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17656    1 TPDAVAVVFENQKLTYRELNERSNQLARFLREKGVKKDSIVAIMMERSAEMIVGILGILKAGGAFVPIDPEYPEERRIYI 80

                         90       100       110
                 ....*....|....*....|....*....|....
gi 489340094  81 LKDSGASLLLTQPGCSAP---NFSGETLEVDMTS 111
Cdd:cd17656   81 MLDSGVRVVLTQRHLKSKlsfNKSTILLEDPSIS 114

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 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd12116    1 PDATAVRDDDRSLSYAELDERANRLAARLRARGVGPGDRVAVYLPRSARLVAAMLAVLKAGAAYVPLDPDYPADRLRYIL 80

                         90
                 ....*....|....*..
gi 489340094  82 KDSGASLLLTQPGCSAP 98
Cdd:cd12116   81 EDAEPALVLTDDALPDR 97

AMP-binding enzyme;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGG-SLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSY 79
Cdd:pfam00501   8 TPDKTALEVGEGrRLTYRELDERANRLAAGLRALGVGKGDRVAILLPNSPEWVVAFLACLKAGAVYVPLNPRLPAEELAY 87

                          90       100
                  ....*....|....*....|
gi 489340094   80 MLKDSGASLLLTQPGCSAPN 99
Cdd:pfam00501  88 ILEDSGAKVLITDDALKLEE 107

peptide synthase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094    1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK12316 3070 TPDAVALAFGEQRLSYAELNRRANRLAHRLIERGVGPDVLVGVAVERSLEMVVGLLAILKAGGAYVPLDPEYPEERLAYM 3149

                          90       100
                  ....*....|....*....|..
gi 489340094   81 LKDSGASLLLTQPGCSAPNFSG 102
Cdd:PRK12316 3150 LEDSGAQLLLSQSHLRLPLAQG 3171

nonribosomal peptide synthase GliP-like; This family includes the adenylation (A) domain of nonribosomal peptide synthases (NRPS) gliotoxin biosynthesis protein P (GliP), thioclapurine biosynthesis protein P (tcpP) and Sirodesmin biosynthesis protein P (SirP). In the filamentous fungus Aspergillus fumigatus, NRPS GliP is involved in the biosynthesis of gliotoxin, which is initiated by the condensation of serine and phenylalanine. Studies show that GliP is not required for invasive aspergillosis, suggesting that the principal targets of gliotoxin are neutrophils or other phagocytes. SirP is a phytotoxin produced by the fungus Leptosphaeria maculans, which causes blackleg disease of canola (Brassica napus). In the fungus Claviceps purpurea, NRPS tcpP catalyzes condensation of tyrosine and glycine, part of biosynthesis of an unusual class of epipolythiodioxopiperazines (ETPs) that lacks the reactive thiol group for toxicity. 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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17653   10 HPDAVAVESLGGSLTYGELDAASNALANRLLQLGVVPGDVVPLLSDRSLEMLVAILAILKAGAAYVPLDAKLPSARIQAI 89

                         90
                 ....*....|.
gi 489340094  81 LKDSGASLLLT 91
Cdd:cd17653   90 LRTSGATLLLT 100

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 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARG-VTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd17648    1 PDRVAVVYGDKRLTYRELNERANRLAHYLLSVAeIRPDDLVGLVLDKSELMIIAILAVWKAGAAYVPIDPSYPDERIQFI 80

                         90
                 ....*....|...
gi 489340094  81 LKDSGASLLLTQP 93
Cdd:cd17648   81 LEDTGARVVITNS 93

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 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:cd05945    4 NPDRPAVVEGGRTLTYRELKERADALAAALASLGLDAGDPVVVYGHKSPDAIAAFLAALKAGHAYVPLDASSPAERIREI 83

                         90
                 ....*....|...
gi 489340094  81 LKDSGASLLLTQP 93
Cdd:cd05945   84 LDAAKPALLIADG 96

acyl-CoA synthetase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK06178  46 RPQRPAIIFYGHVITYAELDELSDRFAALLRQRGVGAGDRVAVFLPNCPQFHIVFFGILKLGAVHVPVSPLFREHELSYE 125

                         90
                 ....*....|..
gi 489340094  81 LKDSGASLLLTQ 92
Cdd:PRK06178 126 LNDAGAEVLLAL 137

acyl-CoA synthetase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   1 TPERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK08316  24 YPDKTALVFGDRSWTYAELDAAVNRVAAALLDLGLKKGDRVAALGHNSDAYALLWLACARAGAVHVPVNFMLTGEELAYI 103

                         90
                 ....*....|....
gi 489340094  81 LKDSGASLLLTQPG 94
Cdd:PRK08316 104 LDHSGARAFLVDPA 117

Malonyl-CoA synthetase (MCS); MCS catalyzes the formation of malonyl-CoA in a two-step reaction consisting of the adenylation of malonate with ATP, followed by malonyl transfer from malonyl-AMP to CoA. Malonic acid and its derivatives are the building blocks of polyketides and malonyl-CoA serves as the substrate of polyketide synthases. Malonyl-CoA synthetase has broad substrate tolerance and can activate a variety of malonyl acid derivatives. MCS may play an important role in biosynthesis of polyketides, the important secondary metabolites with therapeutic and agrochemical utility.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   3 ERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNE-SIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd05941    1 DRIAIVDDGDSITYADLVARAARLANRLLALGKDLRgDRVAFLAPPSAEYVVAQLAIWRAGGVAVPLNPSYPLAELEYVI 80

                 ....*....
gi 489340094  82 KDSGASLLL 90
Cdd:cd05941   81 TDSEPSLVL 89

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 489340094  10 SGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYMLKDSGASLL 89
Cdd:cd05911    7 TGKELTYAQLRTLSRRLAAGLRKLGLKKGDVVGIISPNSTYYPPVFLGCLFAGGIFSAANPIYTADELAHQLKISKPKVI 86

                 ....*.
gi 489340094  90 LTQPGC 95
Cdd:cd05911   87 FTDPDG 92

Prokaryotic long-chain fatty acid CoA synthetases similar to Escherichia coli FadD; This subfamily of the AMP-forming adenylation family contains Escherichia coli FadD and similar prokaryotic fatty acid CoA synthetases. FadD was characterized as a long-chain fatty acid CoA synthetase. The gene fadD is regulated by the fatty acid regulatory protein FadR. Fatty acid CoA synthetase 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:cd05936   13 PDKTALIFMGRKLTYRELDALAEAFAAGLQNLGVQPGDRVALMLPNCPQFPIAYFGALKAGAVVVPLNPLYTPRELEHIL 92

                         90
                 ....*....|
gi 489340094  82 KDSGASLLLT 91
Cdd:cd05936   93 NDSGAKALIV 102

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   2 PERLAIRFSG-----GSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKER 76
Cdd:COG0365   23 GDKVALIWEGedgeeRTLTYAELRREVNRFANALRALGVKKGDRVAIYLPNIPEAVIAMLACARIGAVHSPVFPGFGAEA 102

                         90
                 ....*....|....*...
gi 489340094  77 LSYMLKDSGASLLLTQPG 94
Cdd:COG0365  103 LADRIEDAEAKVLITADG 120

acyl-CoA synthetase; Validated

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYML 81
Cdd:PRK07798  17 PDRVALVCGDRRLTYAELEERANRLAHYLIAQGLGPGDHVGIYARNRIEYVEAMLGAFKARAVPVNVNYRYVEDELRYLL 96

                 ....*....
gi 489340094  82 KDSGASLLL 90
Cdd:PRK07798  97 DDSDAVALV 105

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   2 PERLAIRFSGGSLTYAELDMYASRLAAHLAAR-GVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKERLSYM 80
Cdd:PRK08314  24 PDKTAIVFYGRAISYRELLEEAERLAGYLQQEcGVRKGDRVLLYMQNSPQFVIAYYAILRANAVVVPVNPMNREEELAHY 103

                         90
                 ....*....|.
gi 489340094  81 LKDSGASLLLT 91
Cdd:PRK08314 104 VTDSGARVAIV 114

Uncharacterized acyl-CoA synthetase subfamily similar to Acetoacetyl-CoA synthetase; This uncharacterized acyl-CoA synthetase family (EC 6.2.1.16, or acetoacetate#CoA ligase or acetoacetate:CoA ligase (AMP-forming)) is highly homologous to acetoacetyl-CoA synthetase. However, the proteins in this family exist in only bacteria and archaea. AACS is a cytosolic ligase that specifically activates acetoacetate to its coenzyme A ester by a two-step reaction. Acetoacetate first reacts with ATP to form an acyl-adenylate intermediate, which then reacts with CoA to produce an acyl-CoA ester. This is the first step of the mevalonate pathway of isoprenoid biosynthesis via isopentenyl diphosphate. Isoprenoids are a large class of compounds found in all living organisms.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 489340094   1 TPERLAIRFSG-----GSLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKE 75
Cdd:cd05968   74 TRTRPALRWEGedgtsRTLTYGELLYEVKRLANGLRALGVGKGDRVGIYLPMIPEIVPAFLAVARIGGIVVPIFSGFGKE 153

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 489340094  76 RLSYMLKDSGASLLLTQPGcsapnFSGETLEVDMT 110
Cdd:cd05968  154 AAATRLQDAEAKALITADG-----FTRRGREVNLK 183

L-aminoadipate-semialdehyde dehydrogenase; Members of this protein family are L-aminoadipate-semialdehyde dehydrogenase (EC 1.2.1.31), product of the LYS2 gene. It is also called alpha-aminoadipate reductase. In fungi, lysine is synthesized via aminoadipate. Currently, all members of this family are fungal.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 489340094    13 SLTYAELDMYASRLAAHLAARGVTNESIVGVLSERSPDMLIAVLAVLKAGGAYLPLDPAYPKER 76
Cdd:TIGR03443  270 SFTYKQINEASNILAHYLLKTGIKRGDVVMIYAYRGVDLVVAVMGVLKAGATFSVIDPAYPPAR 333