peptide biosynthesis


Summary: The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.

Top Publications

  1. Bachmann B, Ravel J. Chapter 8. Methods for in silico prediction of microbial polyketide and nonribosomal peptide biosynthetic pathways from DNA sequence data. Methods Enzymol. 2009;458:181-217 pubmed publisher
    ..A bioinformatics tool is presented for rapid preliminary analysis of these modular systems, and prototypical methods for converting these analyses into substructural elements are described. ..
  2. Thoendel M, Horswill A. Identification of Staphylococcus aureus AgrD residues required for autoinducing peptide biosynthesis. J Biol Chem. 2009;284:21828-38 pubmed publisher
    ..These studies provide new insights on the requirements and mechanism of S. aureus AIP biosynthesis. ..
  3. Yu Y, Duan L, Zhang Q, Liao R, Ding Y, Pan H, et al. Nosiheptide biosynthesis featuring a unique indole side ring formation on the characteristic thiopeptide framework. ACS Chem Biol. 2009;4:855-64 pubmed publisher
    ..These results also suggest the feasibility of engineering novel thiopeptides for drug discovery by manipulating the NOS biosynthetic machinery. ..
  4. Lariviere F, Wolfson A, Uhlenbeck O. Uniform binding of aminoacyl-tRNAs to elongation factor Tu by thermodynamic compensation. Science. 2001;294:165-8 pubmed
    ..Because certain misacylated tRNAs bind EF-Tu significantly more strongly or weakly than cognate aa-tRNAs, EF-Tu may contribute to translational accuracy. ..
  5. Walsh C, Chen H, Keating T, Hubbard B, Losey H, Luo L, et al. Tailoring enzymes that modify nonribosomal peptides during and after chain elongation on NRPS assembly lines. Curr Opin Chem Biol. 2001;5:525-34 pubmed
    ..These activities are the province of specialized enzymes (either embedded in the multidomain nonribosomal peptide synthetase structure or standalone). ..
  6. Forster A, Weissbach H, Blacklow S. A simplified reconstitution of mRNA-directed peptide synthesis: activity of the epsilon enhancer and an unnatural amino acid. Anal Biochem. 2001;297:60-70 pubmed
    ..The recombinant clones can be exploited to prepare initiation factors and initiation complexes for structural studies, to study initiation and elongation in ribosomal peptide synthesis, and to screen for eubacterial-specific drugs. ..
  7. Sieber S, Marahiel M. Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chem Rev. 2005;105:715-38 pubmed
  8. Dolan B, Knowlton J, David A, Bennink J, Yewdell J. RNA polymerase II inhibitors dissociate antigenic peptide generation from normal viral protein synthesis: a role for nuclear translation in defective ribosomal product synthesis?. J Immunol. 2010;185:6728-33 pubmed publisher
    ..These data support the idea that Ag processing uses compartmentalized translation, perhaps even in the nucleus itself, to increase the efficiency of the generation of class I peptide ligands. ..
  9. Dolan B, Li L, Veltri C, Ireland C, Bennink J, Yewdell J. Distinct pathways generate peptides from defective ribosomal products for CD8+ T cell immunosurveillance. J Immunol. 2011;186:2065-72 pubmed publisher

Scientific Experts

More Information


  1. Schwartz D, Alijah R, Nussbaumer B, Pelzer S, Wohlleben W. The peptide synthetase gene phsA from Streptomyces viridochromogenes is not juxtaposed with other genes involved in nonribosomal biosynthesis of peptides. Appl Environ Microbiol. 1996;62:570-7 pubmed
    ..By performing immunoblotting experiments, the expression of phsA could be detected in Streptomyces viridochromogenes Tü494 in the stationary-growth phase after 4 days of incubation...
  2. David S, Awasthi S, Balaram P. The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides. J Endotoxin Res. 2000;6:249-56 pubmed
  3. Wurtz N, Turner J, Baird E, Dervan P. Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids. Org Lett. 2001;3:1201-3 pubmed
    ..A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers. ..
  4. Fernandez Patron C, Radomski M, Davidge S. Vascular matrix metalloproteinase-2 cleaves big endothelin-1 yielding a novel vasoconstrictor. Circ Res. 1999;85:906-11 pubmed
    ..These data implicate, for the first time, the endogenous MMP-2/TIMP-2 system in the regulation of vascular reactivity. ..
  5. Shin B, Katoh T, Gutierrez E, Kim J, Suga H, Dever T. Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis. Nucleic Acids Res. 2017;45:8392-8402 pubmed publisher
    ..Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. ..
  6. Aravind L, de Souza R, Iyer L. Predicted class-I aminoacyl tRNA synthetase-like proteins in non-ribosomal peptide synthesis. Biol Direct. 2010;5:48 pubmed publisher
    ..Alternatively they might supply aminoacylated tRNAs for other biosynthetic pathways like that for tetrapyrrole or directly function as peptide ligases as in the case of mycothiol and those identified here. ..
  7. Leppanen A, Penttila L, Renkonen O, McEver R, Cummings R. Glycosulfopeptides with O-glycans containing sialylated and polyfucosylated polylactosamine bind with low affinity to P-selectin. J Biol Chem. 2002;277:39749-59 pubmed
    ..These results demonstrate that contrary to expectations, a core 2 O-glycan containing sialylated PFPL does not promote high affinity binding of PSGL-1 to P-selectin. ..
  8. Kuicke J, Mayer F, Kopperschlager G, Kriegel T. Phosphofructokinase-1 from Saccharomyces cerevisiae: analysis of molecular structure and function by electron microscopy and self-catalysed affinity labelling. Int J Biol Macromol. 1999;24:27-35 pubmed
    ..No stimulation of labelling is observed with proteolytically modified tetrameric 12-S phosphofructokinase. ..
  9. Asakura T, Sugino R, Yao J, Takashima H, Kishore R. Comparative structure analysis of tyrosine and valine residues in unprocessed silk fibroin (silk I) and in the processed silk fiber (silk II) from Bombyx mori using solid-state (13)C,(15)N, and (2)H NMR. Biochemistry. 2002;41:4415-24 pubmed
    ..e., parallel and perpendicular to the magnetic field) solid-state (15)N NMR spectra of biosynthetically labeled [(15)N]Tyr and [(15)N]Val silk fibers reveal the presence of highly oriented semicrystalline regions. ..
  10. Vengadesan K, Anbupalam T, Gautham N. An application of experimental design using mutually orthogonal Latin squares in conformational studies of peptides. Biochem Biophys Res Commun. 2004;316:731-7 pubmed
    ..The results showed that different torsion angles contributed differently to the conformational energy. We are able to identify those parameters that may have to be more carefully considered in conformational studies of peptides. ..
  11. Hodgson D, Sanderson J. The synthesis of peptides and proteins containing non-natural amino acids. Chem Soc Rev. 2004;33:422-30 pubmed
    ..Four complementary approaches are discussed in detail along with examples of their application. The advantages and disadvantages of each technique are also discussed. ..
  12. Silva B, Pinto M, Soares R, Barreto Bergter E, Santos A. Pseudallescheria boydii releases metallopeptidases capable of cleaving several proteinaceous compounds. Res Microbiol. 2006;157:425-32 pubmed
    ..boydii capable of degrading several proteinaceous compounds that could help the fungus to escape from natural human barriers and defenses. ..
  13. Tranchand Bunel D, Auriault C, Diesis E, Gras Masse H. Detection of human antibodies using "convergent" combinatorial peptide libraries or "mixotopes" designed from a nonvariable antigen: application to the EBV viral capsid antigen p18. J Pept Res. 1998;52:495-508 pubmed
  14. Li Q, Lawrence C, Maelor Davies H, Everett N. A tridecapeptide possesses both antimicrobial and protease-inhibitory activities. Peptides. 2002;23:1-6 pubmed
    ..Four other synthetic peptides were tested and the results were suggestive of no correlation between their antimicrobial and protease inhibitory activities. ..
  15. Alves A, Lasaro M, Pyrrho A, Gattass C, de Almeida D, Ferreira L. Antibody response in mice immunized with a plasmid DNA encoding the colonization factor antigen I of enterotoxigenic Escherichia coli. FEMS Immunol Med Microbiol. 1999;23:321-30 pubmed
  16. Wu J, Afar D, Phan H, Witte O, Lam K. Recognition of multiple substrate motifs by the c-ABL protein tyrosine kinase. Comb Chem High Throughput Screen. 2002;5:83-91 pubmed
    ..Our data suggest that protein tyrosine kinases have evolved to recognize multiple substrate motifs. ..
  17. Szabelski M, Stachowiak K, Wiczk W. Influence of organic solvents on papain kinetics. Acta Biochim Pol. 2001;48:1197-201 pubmed
    ..Moreover, the number of papain active sites decreased with the increase of DMF and MeOH concentration. ..
  18. Edwards J, Batiste S, Gibbins E, Goheen S. Synthesis and activity of NH2- and COOH-terminal elastase recognition sequences on cotton. J Pept Res. 1999;54:536-43 pubmed
  19. Tapia V, Bongartz J, Schutkowski M, Bruni N, Weiser A, Ay B, et al. Affinity profiling using the peptide microarray technology: a case study. Anal Biochem. 2007;363:108-18 pubmed
    ..The experimental requirements needed to obtain reliable binding affinity predictions are discussed. ..
  20. Weiser A, Or Guil M, Tapia V, Leichsenring A, Schuchhardt J, Frommel C, et al. SPOT synthesis: reliability of array-based measurement of peptide binding affinity. Anal Biochem. 2005;342:300-11 pubmed
    ..The dissociation constants of the intermediate region were found to be between pK(dis)=5 and pK(dis)=7. Altering the experimental parameters causes a directed change of this region. ..
  21. Tamura K, Schimmel P. Peptide synthesis with a template-like RNA guide and aminoacyl phosphate adaptors. Proc Natl Acad Sci U S A. 2003;100:8666-9 pubmed
    ..No ribosomes or ribozymes were required. Thus, aminoacyl phosphate adaptors and RNA guides could, in principle, have been intermediates in the transition from the RNA world to modern template-dependent protein synthesis. ..
  22. Carrasco N, Hiller D, Strobel S. Minimal transition state charge stabilization of the oxyanion during peptide bond formation by the ribosome. Biochemistry. 2011;50:10491-8 pubmed publisher
    ..This is in contrast to the substantial level of oxyanion stabilization provided by serine proteases. This suggests that the oxyanion may be neutralized via a proton shuttle, resulting in an uncharged transition state. ..
  23. Song Y, Yang S, Lim S, Kim Y, Hahm K, Kim J, et al. Effects of L- or D-Pro incorporation into hydrophobic or hydrophilic helix face of amphipathic alpha-helical model peptide on structure and cell selectivity. Biochem Biophys Res Commun. 2004;314:615-21 pubmed
  24. Matthews J, Young T, Tucker S, Mackay J. The core of the respiratory syncytial virus fusion protein is a trimeric coiled coil. J Virol. 2000;74:5911-20 pubmed
    ..Finally, HR3 forms weak alpha-helical homodimers that do not appear to interact with HR1, HR2, or the HR1-HR2 complex. The results of these studies support the idea that viral fusion proteins have a common core architecture. ..
  25. Kaihatsu K, Braasch D, Cansizoglu A, Corey D. Enhanced strand invasion by peptide nucleic acid-peptide conjugates. Biochemistry. 2002;41:11118-25 pubmed
    ..Rapid strand invasion over a wide range of experimental conditions should further expand the utility of strand invasion by PNAs. ..
  26. Lundberg P, Magzoub M, Lindberg M, Hällbrink M, Jarvet J, Eriksson L, et al. Cell membrane translocation of the N-terminal (1-28) part of the prion protein. Biochem Biophys Res Commun. 2002;299:85-90 pubmed
    ..The secondary structure conversion into beta-structure may be relevant as a seed for the conversion into the scrapie (PrP(Sc)) form of the protein and its amyloidic transformation. ..
  27. Garvin A, Parker K, Haff L. MALDI-TOF based mutation detection using tagged in vitro synthesized peptides. Nat Biotechnol. 2000;18:95-7 pubmed
    ..The process can be multiplexed and is amenable to automation, providing an efficient, high-throughput means for mutation discovery and genetic profiling. ..
  28. Tasiemski A, Vandenbulcke F, Mitta G, Lemoine J, Lefebvre C, Sautiere P, et al. Molecular characterization of two novel antibacterial peptides inducible upon bacterial challenge in an annelid, the leech Theromyzon tessulatum. J Biol Chem. 2004;279:30973-82 pubmed
  29. Yarus M. Amino acids as RNA ligands: a direct-RNA-template theory for the code's origin. J Mol Evol. 1998;47:109-17 pubmed
    ..Such findings are comprehensively reviewed, and the implications for the origin of coded peptide synthesis are considered. An origins hypothesis which accommodates all the data, DRT (direct RNA templating), is formulated. ..
  30. Deechongkit S, You S, Kelly J. Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis. Org Lett. 2004;6:497-500 pubmed
  31. Shin S, Yang S, Park E, Eom S, Song W, Kim Y, et al. Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18. Biochem Biophys Res Commun. 2002;290:558-62 pubmed
    ..Thus, these results support that P18 may prove to be a salt-resistant antibiotic peptide potentially useful in the treatment of cystic fibrosis patients as well as a valuable adjuvant for antimicrobial chemotherapy. ..
  32. Chen P, Lin C, Chang Y, Lin S, Chan S. One O-linked sugar can affect the coil-to-beta structural transition of the prion peptide. Proc Natl Acad Sci U S A. 2002;99:12633-8 pubmed
    ..Moreover, this effect is sugar specific. Replacing alpha-GalNAc with beta-GlcNAc does not yield the same effect. ..
  33. Buerger C, Groner B. Bifunctional recombinant proteins in cancer therapy: cell penetrating peptide aptamers as inhibitors of growth factor signaling. J Cancer Res Clin Oncol. 2003;129:669-75 pubmed
    ..The aptamer constructs can be supplemented with additional functional domains to enhance their inhibitory effects. ..
  34. White P, Keyte J, Bailey K, Bloomberg G. Expediting the Fmoc solid phase synthesis of long peptides through the application of dimethyloxazolidine dipeptides. J Pept Sci. 2004;10:18-26 pubmed
    ..However, by the judicious use of dimethyloxazolidine dipeptides of serine and threonine, the peptide could be readily prepared in remarkable purity by applying single 1 h coupling reactions. ..
  35. Umehara T, Kitagawa T, Nakazawa Y, Yoshino H, Nemoto R, Tamura K. RNA tetraplex as a primordial peptide synthesis scaffold. Biosystems. 2012;109:145-50 pubmed publisher
    ..Using supportive experimental data, we discuss the origin and evolution of peptide bond formation in early biological systems. ..
  36. Shao W, Fernandez E, Sachpatzidis A, Wilken J, Thompson D, Schweitzer B, et al. CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure. Eur J Biochem. 2001;268:2948-59 pubmed
    ..We propose that vMIP-II was initially specific for CCR5 and acquired receptor-binding properties to CCR2 and other chemokine receptors. ..
  37. Avrahami D, Shai Y. A new group of antifungal and antibacterial lipopeptides derived from non-membrane active peptides conjugated to palmitic acid. J Biol Chem. 2004;279:12277-85 pubmed
  38. Fuchise T, Kishimura H, Yang Z, Kojoma M, Toyota E, Sekizaki H. Atlantic cod trypsin-catalyzed peptide synthesis with inverse substrates as acyl donor components. Chem Pharm Bull (Tokyo). 2010;58:484-7 pubmed
    ..The enzymatic hydrolysis of the resulting products was negligible. ..
  39. Niidome T, Urakawa M, Takaji K, Matsuo Y, Ohmori N, Wada A, et al. Influence of lipophilic groups in cationic alpha-helical peptides on their abilities to bind with DNA and deliver genes into cells. J Pept Res. 1999;54:361-7 pubmed
    ..These results indicate that consideration of total hydrophobicity balance is needed for the design of an efficient gene carrier peptide. ..
  40. Truckenmiller M, Princiotta M, Norbury C, Bonneau R. Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation. J Neuroimmunol. 2005;160:48-60 pubmed
    ..At the most fundamental cellular level, this impairment of antigen processing has implications for the regulation of protein degradation in all cells, which is critical to many aspects of immune function...
  41. Schmoock G, Pfennig F, Jewiarz J, Schlumbohm W, Laubinger W, Schauwecker F, et al. Functional cross-talk between fatty acid synthesis and nonribosomal peptide synthesis in quinoxaline antibiotic-producing streptomycetes. J Biol Chem. 2005;280:4339-49 pubmed publisher
    ..These data show for the first time a functional interaction between nonribosomal peptide synthesis and fatty acid synthesis...
  42. Sciorra V, Rudge S, Wang J, McLaughlin S, Engebrecht J, Morris A. Dual role for phosphoinositides in regulation of yeast and mammalian phospholipase D enzymes. J Cell Biol. 2002;159:1039-49 pubmed
    ..Phosphoinositides therefore have a dual role in PLD regulation: membrane targeting mediated by the PH domain and stimulation of catalysis mediated by the polybasic motif. ..
  43. Pearson L, Moffitt M, Ginn H, B A N. The molecular genetics and regulation of cyanobacterial peptide hepatotoxin biosynthesis. Crit Rev Toxicol. 2008;38:847-56 pubmed
    ..Understanding the role of cyanotoxins in the producing microorganisms and the environmental regulation of their biosynthesis genes may also suggest the means of controlling toxic-bloom events. ..
  44. Carotti A, Carrieri A, Cellamare S, Fanizzi F, Gavuzzo E, Mazza F. Extended form of a retro-inverso peptide stabilized by beta-sheet unidirectional H-bonds: Crystallographic and NMR evidence. Biopolymers. 2001;60:322-32 pubmed
    ..H==N H-bonds per residue. ..
  45. Kuromatsu I, Matsuo K, Takamura S, Kim G, Takebe Y, Kawamura J, et al. Induction of effective antitumor immune responses in a mouse bladder tumor model by using DNA of an alpha antigen from mycobacteria. Cancer Gene Ther. 2001;8:483-90 pubmed
    ..The results of this study provided evidence of the potential usefulness of alpha Ag in tumor cell vaccines. ..
  46. Ramachandiran V, Willms C, Kramer G, Hardesty B. Fluorophores at the N terminus of nascent chloramphenicol acetyltransferase peptides affect translation and movement through the ribosome. J Biol Chem. 2000;275:1781-6 pubmed
    ..This finding is in agreement with recent data showing cross-linking of the N terminus of nascent peptides to nucleotides of the 23 S ribosomal RNA. ..
  47. Witkowska R, Kaczmarek K, Crisma M, Toniolo C, Zabrocki J. C(alpha)-hydroxymethyl methionine: synthesis, optical resolution and crystal structure of its (+)-N(alpha)-benzoyl derivative. J Pept Sci. 2001;7:619-25 pubmed
    ..In addition, the X-ray diffraction analysis showed that the C(alpha,alpha)-disubstituted glycyl residue adopts the fully extended (C5) conformation. ..
  48. Adessi C, Frossard M, Boissard C, Fraga S, Bieler S, Ruckle T, et al. Pharmacological profiles of peptide drug candidates for the treatment of Alzheimer's disease. J Biol Chem. 2003;278:13905-11 pubmed
    ..Our results suggest that the pharmacological profile of beta-sheet breaker peptides can be improved to produce compounds with drug-like properties that might offer a new promise in the treatment of Alzheimer's disease. ..
  49. Shaw W, Campbell A, Paine M, Snead M. The COOH terminus of the amelogenin, LRAP, is oriented next to the hydroxyapatite surface. J Biol Chem. 2004;279:40263-6 pubmed
    ..The experimental results provide direct evidence orienting the charged COOH-terminal region of the amelogenin protein on the HAP surface, optimized to exert control on developing enamel crystals. ..
  50. Loughnan M, Alewood P. Physico-chemical characterization and synthesis of neuronally active alpha-conotoxins. Eur J Biochem. 2004;271:2294-304 pubmed
  51. Zanker D, Waithman J, Yewdell J, Chen W. Mixed proteasomes function to increase viral peptide diversity and broaden antiviral CD8+ T cell responses. J Immunol. 2013;191:52-9 pubmed publisher
    ..These findings indicate that mixed proteasomes function to enhance the diversity of peptides and support a broad CD8(+) T cell response. ..
  52. Butterfield L, Ribas A, Dissette V, Amarnani S, Vu H, Oseguera D, et al. Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin Cancer Res. 2003;9:998-1008 pubmed
  53. Yamamoto Y, Usuki H, Iwabuchi M, Hatanaka T. Prolyl aminopeptidase from Streptomyces thermoluteus subsp. fuscus strain NBRC14270 and synthesis of proline-containing peptides by its S144C variant. Appl Environ Microbiol. 2010;76:6180-5 pubmed publisher
    ..These findings support the use of PAPs as a tool for production of physiologically active proline peptides. ..