Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces actuosus leads to increased production of nosiheptide

  • 344 Accesses

  • 14 Citations


S-Adenosylmethionine (SAM) is synthesized via the metabolic reaction involving adenosine triphosphate and l-methionine that is catalyzed by the enzyme S-adenosyl-l-methionine synthetase (SAM-s) and encoded by the gene metK. In the present study, metK with the absence of introns from Saccharomyces cerevisiae was introduced into Streptomyces actuosus, a nosiheptide (Nsh) producer. Intracellular SAM levels were determined by high-pressure liquid chromatography. Through optimizing the nutrient content of the medium, it was shown that increased SAM production induced by the overexpression of SAM-s leads to an increase in the intracellular cysteine pool and overproduction of Nsh in S. actuosus. This investigation shows that increased SAM promotes the elevated production of the non-ribosomal thiopeptide Nsh in Streptomyces sp.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7


  1. Cathryn ASH, Neil LK, Heather CJ, Amy MG, Christian B, Christopher TW (1999) Assembly line enzymology by multimodular nonribosomal peptide synthetases: the thioesterase domain of E. coli EntF catalyzes both elongation and cyclolactonization. Chem Biol 6:385–400

  2. David EC, Walsh C (1999) The parallel and convergent universes of polyketide synthases and nonribosomal peptide synthetases. Chem Biol 6:R319–R325

  3. Huh JH, Kim DJ, Zhao XQ, Li M, Jo YY, Yoon YM, Shin SK (2004) Widespread activation of antibiotic biosynthesis by S-adenosylmethionine in Streptomycetes. FEMS Microbiol Lett 238:439–447

  4. Kim DJ, Huh JH, Yang YY, Kang CM, Lee IH, Hyun CG, Hong SK, Suh JW (2003) Accumulation of S-adenosyl-l-methionine enhances production of actinorhodin but inhibits sporulation in Streptomyces lividans TK23. J Bacteriol 185:592–600

  5. Mocek U, Chen LC, Keller PJ, Houck DR, Beale JM, Floss HG (1989) Proton and carbon-13 NMR assignments of the thiopeptide antibiotic nosiheptide. J Antibiotics 42:1643–1648

  6. Mocek U, Knaggs AR, Tsuchiga R, Ngugen T, Beale JM, Floss HG (1993) Biosynthesis of modified peptide antibiotic nosiheptide in Streptomyces actuosus. J Am Chem Soc 115:7557–7568

  7. Nakajima A, Wada K, Katayama K, Saubermann L, Osawa E, Nagase H, Ueno N, Matsuhashi N, Aburatani H (2002) Gene expression profile after peroxisome proliferator activator receptor-gamma ligand administration in dextran sodium sulfate mice. J Gastroenterol 37(14):62–66

  8. Williamson JM, Meyer R, Inamine E (1985) Reverse transsulfuration and its relationship to thienamycin biosynthesis in Streptomyces cattleya. Antimicrob Agents Chemother 28(4):478

  9. Yoon GS, Ko KH, Kang HW, Suh JW, Kim YS, Ryu YW (2006) Characterization of S-adenosylmethionine synthetase from Streptomyces avermitilis NRRL8165 and its effect on antibiotic production. Enzym Microb Tech 39:466–473

Download references

Author information

Correspondence to Linquan Bai or Pei Zhou.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhang, X., Fen, M., Shi, X. et al. Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces actuosus leads to increased production of nosiheptide. Appl Microbiol Biotechnol 78, 991–995 (2008). https://doi.org/10.1007/s00253-008-1394-5

Download citation


  • Streptomyces actuosus
  • S-Adenosylmethionine
  • metK
  • Cysteine
  • Nosiheptide