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 2321274741   6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:cd12117     2 LFEEQAARTPDAVAVVYGDRSLTYAELNERANRLARRLRAAGVGPGDVVGVLAERSPELVVALLAVLKAGAAYVPLDPEL 81

                  ....*
gi 2321274741  86 PDARV 90
Cdd:cd12117    82 PAERL 86

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  28 SYRELDEASNRLAHLLVSE-GAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:TIGR01733   1 TYRELDERANRLARHLRAAgGVGPGDRVAVLLERSAELVVAILAVLKAGAAYVPLDPAYPAERL 64

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 2321274741   6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:cd12117     2 LFEEQAARTPDAVAVVYGDRSLTYAELNERANRLARRLRAAGVGPGDVVGVLAERSPELVVALLAVLKAGAAYVPLDPEL 81

                  ....*
gi 2321274741  86 PDARV 90
Cdd:cd12117    82 PAERL 86

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 2321274741   6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:cd17646     3 LVAEQAARTPDAPAVVDEGRTLTYRELDERANRLAHLLRARGVGPEDRVAVLLPRSADLVVALLAVLKAGAAYLPLDPGY 82

                  ....*
gi 2321274741  86 PDARV 90
Cdd:cd17646    83 PADRL 87

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2321274741  15 PDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd17643     1 PEAVAVVDEDRRLTYGELDARANRLARTLRAEGVGPGDRVALALPRSAELIVALLAILKAGGAYVPIDPAYPVERI 76

similar to adenylation domain of chondramide synthase cmdD; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) includes phosphinothricin tripeptide (PTT, phosphinothricylalanylalanine) synthetase, where PTT is a natural-product antibiotic and potent herbicide that is produced by Streptomyces hygroscopicus. This adenylation domain has been confirmed to directly activate beta-tyrosine, and fluorinated chondramides are produced through precursor-directed biosynthesis. Also included in this family is chondramide synthase D (also known as ATP-dependent phenylalanine adenylase or phenylalanine activase or tyrosine activase). Chondramides A-D are depsipeptide antitumor and antifungal antibiotics produced by C. crocatus, are a class of mixed peptide/polyketide depsipeptides comprised of three amino acids (alanine, N-methyltryptophan, plus the unusual amino acid beta-tyrosine or alpha-methoxy-beta-tyrosine) and a polyketide chain ([E]-7-hydroxy-2,4,6-trimethyloct-4-enoic acid).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2321274741  15 PDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd17652     1 PDAPAVVFGDETLTYAELNARANRLARLLAARGVGPERLVALALPRSAELVVAILAVLKAGAAYLPLDPAYPAERI 76

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK12467  3100 LIEAQVARTPEAPALVFGDQQLSYAELNRRANRLAHRLIAIGVGPDVLVGVAVERSVEMIVALLAVLKAGGAYVPLDPEY 3179

                   ....
gi 2321274741   86 PDAR 89
Cdd:PRK12467  3180 PRER 3183

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 2321274741   6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:cd17645     3 LFEEQVERTPDHVAVVDRGQSLTYKQLNEKANQLARHLRGKGVKPDDQVGIMLDKSLDMIAAILGVLKAGGAYVPIDPDY 82

                  ....*
gi 2321274741  86 PDARV 90
Cdd:cd17645    83 PGERI 87

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 2321274741   6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:cd17653     2 AFERIAAAHPDAVAVESLGGSLTYGELDAASNALANRLLQLGVVPGDVVPLLSDRSLEMLVAILAILKAGAAYVPLDAKL 81

                  ....*
gi 2321274741  86 PDARV 90
Cdd:cd17653    82 PSARI 86

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK12316  4556 LVAERARMTPDAVAVVFDEEKLTYAELNRRANRLAHALIARGVGPEVLVGIAMERSAEMMVGLLAVLKAGGAYVPLDPEY 4635

                   ....*
gi 2321274741   86 PDARV 90
Cdd:PRK12316  4636 PRERL 4640

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK12316  2008 RIAEQAARAPEAIAVVFGDQHLSYAELDSRANRLAHRLRARGVGPEVRVAIAAERSFELVVALLAVLKAGGAYVPLDPNY 2087

                   ....*
gi 2321274741   86 PDARV 90
Cdd:PRK12316  2088 PAERL 2092

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  28 SYRELDEASNRLAHLLVSE-GAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:TIGR01733   1 TYRELDERANRLARHLRAAgGVGPGDRVAVLLERSAELVVAILAVLKAGAAYVPLDPAYPAERL 64

peptide synthase; Validated

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK05691  2193 LFAAQAARTPQAPALTFAGQTLSYAELDARANRLARALRERGVGPQVRVGLALERSLEMVVGLLAILKAGGAYVPLDPEY 2272

                   ....*
gi 2321274741   86 PDARV 90
Cdd:PRK05691  2273 PLERL 2277

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK12316   516 LFEEQVERTPEAPALAFGEETLDYAELNRRANRLAHALIERGVGPDVLVGVAMERSIEMVVALLAILKAGGAYVPLDPEY 595

                   ....*
gi 2321274741   86 PDARV 90
Cdd:PRK12316   596 PAERL 600

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2321274741  15 PDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd17650     1 PDAIAVSDATRQLTYRELNERANQLARTLRGLGVAPGSVVGVCADRSLDAIVGLLAVLKAGGAYVPIDPDYPAERL 76

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2321274741  15 PDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAG-PGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd17648     1 PDRVAVVYGDKRLTYRELNERANRLAHYLLSVAEIrPDDLVGLVLDKSELMIIAILAVWKAGAAYVPIDPSYPDERI 77

peptide synthase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    6 LFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMH 85
Cdd:PRK12316  3062 LFEEQVERTPDAVALAFGEQRLSYAELNRRANRLAHRLIERGVGPDVLVGVAVERSLEMVVGLLAILKAGGAYVPLDPEY 3141

                   ....
gi 2321274741   86 PDAR 89
Cdd:PRK12316  3142 PEER 3145

peptide synthase; Validated

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741    3 IPVLFAAQVARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPID 82
Cdd:PRK05691  1133 LPELLNEQARQTPERIALVWDGGSLDYAELHAQANRLAHYLRDKGVGPDVCVAIAAERSPQLLVGLLAILKAGGAYVPLD 1212

                   ....*...
gi 2321274741   83 PMHPDARV 90
Cdd:PRK05691  1213 PDYPAERL 1220

The adenylation domain of nonribosomal peptide synthetases (NRPS), including Streptoalloteichus tallysomycin biosynthesis genes; 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 TLM biosynthetic gene cluster from Streptoalloteichus that consists of nine NRPS genes; the N-terminal module of TlmVI (NRPS-5) and the starter module of BlmVI (NRPS-5) are comprised of the acyl CoA ligase (AL) and acyl carrier protein (ACP)-like domains, which are thought to be involved in the biosynthesis of the beta-aminoalaninamide moiety.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2321274741  15 PDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd12114     1 PDATAVICGDGTLTYGELAERARRVAGALKAAGVRPGDLVAVTLPKGPEQVVAVLGILAAGAAYVPVDIDQPAARR 76

malonyl-CoA synthase; Validated

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2321274741   6 LFAAQVARVPDAVAVSFE---GRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLP 80
Cdd:PRK07514    5 LFDALRAAFADRDAPFIEtpdGLRYTYGDLDAASARLANLLVALGVKPGDRVAVQVEKSPEALALYLATLRAGAVFLP 82

fatty acyl-CoA synthetase, including FadD13; This family contains fatty acyl-CoA synthetases, including Mycobacterium tuberculosis acid-induced operon MymA encoding the fatty acyl-CoA synthetase FadD13 which is essential for virulence and intracellular growth of the pathogen. The fatty acyl-CoA synthetase activates lipids before entering into the metabolic pathways and is also involved in transmembrane lipid transport. However, unlike soluble fatty acyl-CoA synthetases, but like the mammalian integral-membrane very-long-chain acyl-CoA synthetases, FadD13 accepts lipid substrates up to the maximum length of C26, and this is facilitated by an extensive hydrophobic tunnel from the active site to a positively charged patch. Also included is feruloyl-CoA synthetase (Fcs) in Rhodococcus strains where it is involved in biotechnological vanillin production from eugenol and ferulic acid via a non-beta-oxidative pathway.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  11 VARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPM 84
Cdd:cd17631     5 ARRHPDRTALVFGGRSLTYAELDERVNRLAHALRALGVAKGDRVAVLSKNSPEFLELLFAAARLGAVFVPLNFR 78

acyl-CoA synthetase; Validated

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2321274741  13 RVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPM 84
Cdd:PRK06178   45 ERPQRPAIIFYGHVITYAELDELSDRFAALLRQRGVGAGDRVAVFLPNCPQFHIVFFGILKLGAVHVPVSPL 116

acyl-CoA synthetase; Validated

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  11 VARVPDAVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPM 84
Cdd:PRK08316   21 ARRYPDKTALVFGDRSWTYAELDAAVNRVAAALLDLGLKKGDRVAALGHNSDAYALLWLACARAGAVHVPVNFM 94

Alpha-aminoadipate reductase; This family contains L-2-aminoadipate reductase, also known as alpha-aminoadipate reductase (EC 1.2.1.95) or alpha-AR or L-aminoadipate-semialdehyde dehydrogenase (EC 1.2.1.31), which catalyzes the activation of alpha-aminoadipate by ATP-dependent adenylation and the reduction of activated alpha-aminoadipate by NADPH. The activated alpha-aminoadipate is bound to the phosphopantheinyl group of the enzyme itself before it is reduced to (S)-2-amino-6-oxohexanoate.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2321274741  25 RSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDAR 89
Cdd:cd17647    19 RSFTYRDINEASNIVAHYLIKTGIKRGDVVMIYSYRGVDLMVAVMGVLKAGATFSVIDPAYPPAR 83

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2321274741  11 VARVPDAVAVSFEG-----RSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPM 84
Cdd:COG0365    19 AEGRGDKVALIWEGedgeeRTLTYAELRREVNRFANALRALGVKKGDRVAIYLPNIPEAVIAMLACARIGAVHSPVFPG 97

acyl-CoA synthetase; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2321274741  11 VARVPD--AVAVSFEGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPI 81
Cdd:PRK13391    7 AQTTPDkpAVIMASTGEVVTYRELDERSNRLAHLFRSLGLKRGDHVAIFMENNLRYLEVCWAAERSGLYYTCV 79

acyl-CoA synthetase family member 4; This family of the adenylation (A) domain of nonribosomal peptide synthases (NRPS) contains acyl-CoA synthethase family member 4, also known as 2-aminoadipic 6-semialdehyde dehydrogenase or aminoadipate-semialdehyde dehydrogenase, most of which are uncharacterized. Acyl-CoA synthetase catalyzes the initial reaction in fatty acid metabolism, by forming a thioester with CoA. 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 2321274741  15 PDAVAVSFEGR----SVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPMHPDARV 90
Cdd:cd17654     1 PDRPALIIDQTtsdtTVSYADLAEKISNLSNFLRKKFQTEERAIGLRCDRGTESPVAILAILFLGAAYAPIDPASPEQRS 80

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  12 ARVPDAVAVSFEGRSVSYRELDEASNRLA-HLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDPM 84
Cdd:PRK08314   21 RRYPDKTAIVFYGRAISYRELLEEAERLAgYLQQECGVRKGDRVLLYMQNSPQFVIAYYAILRANAVVVPVNPM 94

Long-chain acyl-CoA synthetase (AMP-forming) [Lipid transport and metabolism];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2321274741   2 SIPVLFAAQVARVPDAVAVSF----EGRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAA 77
Cdd:COG1022    12 TLPDLLRRRAARFPDRVALREkedgIWQSLTWAEFAERVRALAAGLLALGVKPGDRVAILSDNRPEWVIADLAILAAGAV 91

                  ....*.
gi 2321274741  78 YLPIDP 83
Cdd:COG1022    92 TVPIYP 97

Fatty acid transport proteins (FATP) play dual roles as fatty acid transporters and its activation enzymes; Fatty acid transport protein (FATP) transports long-chain or very-long-chain fatty acids across the plasma membrane. FATPs also have fatty acid CoA synthetase activity, thus playing dual roles as fatty acid transporters and its activation enzymes. At least five copies of FATPs are identified in mammalian cells. This family also includes prokaryotic FATPs. FATPs are the key players in the trafficking of exogenous fatty acids into the cell and in intracellular fatty acid homeostasis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2321274741  24 GRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAA 77
Cdd:cd05940     1 DEALTYAELDAMANRYARWLKSLGLKPGDVVALFMENRPEYVLLWLGLVKIGAV 54

medium-chain fatty-acid--CoA ligase;

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2321274741   7 FAAQVARVPDAVAVSFE-GRSVSYRELDEASNRLAHLLVSEGAGPGRCVALLVNRSVEAIVSILAVLKSGAAYLPIDP 83
Cdd:PRK06087   29 WQQTARAMPDKIAVVDNhGASYTYSALDHAASRLANWLLAKGIEPGDRVAFQLPGWCEFTIIYLACLKVGAVSVPLLP 106