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Alamethicin^[1]
Names
	IUPAC name N-acetyl-2-methylalanyl-L-prolyl-2-methylalanyl-L-alanyl-2-methylalanyl-L-alanyl-L-glutaminyl-2-methylalanyl-L-valyl-2-methylalanylglycyl-L-leucyl-2-methylalanyl-L-prolyl-L-valyl-2-methylalanyl-2-methylalanyl-L-α-glutamyl-N1-[(1S)-1-benzyl-2-hydroxyethyl]-L-glutamamide
Identifiers
CAS Number	27061-78-5 ;
3D model (JSmol)	Interactive image; Interactive image;
ChEMBL	ChEMBL438243 ;
ChemSpider	17288702 ;
ECHA InfoCard	100.121.626
PubChem CID	16132042;
UNII	0LT1I1B7S8 ;
CompTox Dashboard (EPA)	DTXSID40893675 ;
	InChI InChI=1S/C92H150N22O25/c1-47(2)43-58(72(127)108-92(24,25)84(139)113-41-29-33-59(113)73(128)103-65(48(3)4)75(130)111-90(20,21)82(137)112-89(18,19)80(135)102-56(37-40-64(120)121)70(125)101-55(35-38-61(93)117)69(124)98-54(46-115)44-53-31-27-26-28-32-53)99-63(119)45-95-77(132)85(10,11)110-76(131)66(49(5)6)104-81(136)88(16,17)107-71(126)57(36-39-62(94)118)100-67(122)50(7)96-78(133)86(12,13)106-68(123)51(8)97-79(134)87(14,15)109-74(129)60-34-30-42-114(60)83(138)91(22,23)105-52(9)116/h26-28,31-32,47-51,54-60,65-66,115H,29-30,33-46H2,1-25H3,(H2,93,117)(H2,94,118)(H,95,132)(H,96,133)(H,97,134)(H,98,124)(H,99,119)(H,100,122)(H,101,125)(H,102,135)(H,103,128)(H,104,136)(H,105,116)(H,106,123)(H,107,126)(H,108,127)(H,109,129)(H,110,131)(H,111,130)(H,112,137)(H,120,121)/t50-,51-,54-,55-,56-,57-,58-,59-,60-,65-,66-/m0/s1 Key: LGHSQOCGTJHDIL-UTXLBGCNSA-N ; InChI=1/C92H150N22O25/c1-47(2)43-58(72(127)108-92(24,25)84(139)113-41-29-33-59(113)73(128)103-65(48(3)4)75(130)111-90(20,21)82(137)112-89(18,19)80(135)102-56(37-40-64(120)121)70(125)101-55(35-38-61(93)117)69(124)98-54(46-115)44-53-31-27-26-28-32-53)99-63(119)45-95-77(132)85(10,11)110-76(131)66(49(5)6)104-81(136)88(16,17)107-71(126)57(36-39-62(94)118)100-67(122)50(7)96-78(133)86(12,13)106-68(123)51(8)97-79(134)87(14,15)109-74(129)60-34-30-42-114(60)83(138)91(22,23)105-52(9)116/h26-28,31-32,47-51,54-60,65-66,115H,29-30,33-46H2,1-25H3,(H2,93,117)(H2,94,118)(H,95,132)(H,96,133)(H,97,134)(H,98,124)(H,99,119)(H,100,122)(H,101,125)(H,102,135)(H,103,128)(H,104,136)(H,105,116)(H,106,123)(H,107,126)(H,108,127)(H,109,129)(H,110,131)(H,111,130)(H,112,137)(H,120,121)/t50-,51-,54-,55-,56-,57-,58-,59-,60-,65-,66-/m0/s1 Key: LGHSQOCGTJHDIL-UTXLBGCNBC;
	SMILES CC(C)C[C@@H](C(=O)NC(C)(C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)NC(C)(C)C(=O)NC(C)(C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC2=CC=CC=C2)CO)NC(=O)CNC(=O)C(C)(C)NC(=O)[C@H](C(C)C)NC(=O)C(C)(C)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](C)NC(=O)C(C)(C)NC(=O)[C@H](C)NC(=O)C(C)(C)NC(=O)[C@@H]3CCCN3C(=O)C(C)(C)NC(=O)C; CC(C)CC(C(=O)NC(C)(C)C(=O)N1CCCC1C(=O)NC(C(C)C)C(=O)NC(C)(C)C(=O)NC(C)(C)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)N)C(=O)NC(Cc2ccccc2)CO)NC(=O)CNC(=O)C(C)(C)NC(=O)C(C(C)C)NC(=O)C(C)(C)NC(=O)C(CCC(=O)N)NC(=O)C(C)NC(=O)C(C)(C)NC(=O)C(C)NC(=O)C(C)(C)NC(=O)C3CCCN3C(=O)C(C)(C)NC(=O)C;
Properties
Chemical formula	C92H150N22O25
Molar mass	1964.31 g/mol
Appearance	Off white solid
Melting point	255 to 270 °C (491 to 518 °F; 528 to 543 K)
Solubility in water	Insoluble
Solubility in DMSO, methanol, ethanol	Soluble
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Alamethicin is a channel-forming peptide antibiotic, produced by the fungus Trichoderma viride. It belongs to peptaibol peptides which contain the non-proteinogenic amino acid residue Aib (2-aminoisobutyric acid). This residue strongly induces formation of alpha-helical structure. The peptide sequence is

Ac-Aib-Pro-Aib-Ala-Aib-Ala-Gln-Aib-Val-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu-Gln-Phl

where Ac = acetyl, Phl = phenylalaninol, and Aib = 2-Aminoisobutyric acid.

In cell membranes, it forms voltage-dependent ion channels by aggregation of four to six molecules.

Biosynthesis

Alamethicin biosynthesis is hypothesized to be catalyzed by alamethicin synthase, a Nonribosomal peptide synthase (NRPS) first isolated in 1975.^[2] Although there are several sequences of the alamethicin peptide accepted,^[3] evidence suggests these all follow the general NRPS mechanism ^[4] with small variations at select amino acids.^[5] Beginning with the acylation of the N terminal of the first aminoisobutiric acid on the ALM synthase enzyme by Acetyl-CoA,^[6] this is followed by the sequential condensation of amino acids by each modular unit of the synthetase.^[7] Amino acids are initially adenylated by an “adenylylation” (A) domain before being attached by a thioester bond to an Acyl Carrier Protein-like Peptidyl carrier protein.^[8] The growing chain is attached to the amino acid bearing PCP by the "condensation" (C) domain, followed by another round of the same reactions by the next module.^[8]

Assembly is completed by the addition of phenylalaninol, an unusual amino acid-like substrate.^[9] Following addition of phenylalaninol the completed peptide chain is cleaved by the thioesterase domain, cleaving the thioester bond and leaving an alcohol.^{[citation needed]}

References

^ Alamethicin product page from Fermentek
^ Rindfleisch, H.; Kleinkauf, H. (1976-03-01). "Biosynthesis of alamethicin". FEBS Letters. 62 (3): 276–280. doi:10.1016/0014-5793(76)80074-9. ISSN 0014-5793. PMID 945191.
^ Kirschbaum, Jochen; Krause, Corina; Winzheimer, Ruth K.; Brückner, Hans (November–December 2003). "Sequences of alamethicins F30 and F50 reconsidered and reconciled". Journal of Peptide Science. 9 (11–12): 799–809. doi:10.1002/psc.535. ISSN 1075-2617. PMID 14658799. S2CID 25076336.
^ Marahiel, Mohamed A.; Stachelhaus, Torsten; Mootz, Henning D. (1997-11-01). "Modular Peptide Synthetases Involved in Nonribosomal Peptide Synthesis". Chemical Reviews. 97 (7): 2651–2674. doi:10.1021/cr960029e. ISSN 0009-2665. PMID 11851476.
^ Kleinkauf, H.; Rindfleisch, H. (1975). "Non-ribosomal biosynthesis of the cyclic octadecapeptide alamethicin". Acta Microbiologica Academiae Scientiarum Hungaricae. 22 (4): 411–418. ISSN 0001-6187. PMID 1241650.
^ Mohr, H.; Kleinkauf, H. (1978-10-12). "Alamethicin biosynthesis: acetylation of the amino terminus and attachment of phenylalaninol". Biochimica et Biophysica Acta (BBA) - Enzymology. 526 (2): 375–386. doi:10.1016/0005-2744(78)90129-8. ISSN 0006-3002. PMID 568941.
^ Weber, Thomas; Marahiel, Mohamed A (January 2001). "Exploring the Domain Structure of Modular Nonribosomal Peptide Synthetases". Structure. 9 (1): –3–R9. doi:10.1016/S0969-2126(00)00560-8. ISSN 0969-2126. PMID 11342140.
^ ^a ^b Fischbach, Michael A.; Walsh, Christopher T. (August 2006). "Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms". Chemical Reviews. 106 (8): 3468–3496. doi:10.1021/cr0503097. ISSN 0009-2665. PMID 16895337.
^ Turner, S. Richard; Voit, Brigitte I.; Mourey, Thomas H. (1993-08-01). "All-aromatic hyperbranched polyesters with C-phenylalaninol and N-acetate end groups: synthesis and characterization". Macromolecules. 26 (17): 4617–4623. Bibcode:1993MaMol..26.4617T. doi:10.1021/ma00069a031. ISSN 0024-9297.