Identification of a Gene Involved in the Synthesis of a Dipeptidyl Peptidase IV Inhibitor in Aspergillus Oryzae

Overview

Journal Appl Environ Microbiol

Specialties Environmental Health
Microbiology

Date 2012 Jul 31

PMID 22843525

Citations 6

Authors

Kazuhiko Imamura

Yoshihito Tsuyama

Terukage Hirata

Sumihiro Shiraishi

Kazutoshi Sakamoto

Osamu Yamada

Osamu Akita

Hitoshi Shimoi

Affiliations

Soon will be listed here.

Abstract

WYK-1 is a dipeptidyl peptidase IV inhibitor produced by Aspergillus oryzae strain AO-1. Because WYK-1 is an isoquinoline derivative consisting of three l-amino acids, we hypothesized that a nonribosomal peptide synthetase was involved in its biosynthesis. We identified 28 nonribosomal peptide synthetase genes in the sequenced genome of A. oryzae RIB40. These genes were also identified in AO-1. Among them, AO090001000009 (wykN) was specifically expressed under WYK-1-producing conditions in AO-1. Therefore, we constructed wykN gene disruptants of AO-1 after nonhomologous recombination was suppressed by RNA interference to promote homologous recombination. Our results demonstrated that the disruptants did not produce WYK-1. Furthermore, the expression patterns of 10 genes downstream of wykN were similar to the expression pattern of wykN under several conditions. Additionally, homology searches revealed that some of these genes were predicted to be involved in WYK-1 biosynthesis. Therefore, we propose that wykN and the 10 genes identified in this study constitute the WYK-1 biosynthetic gene cluster.

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References

Holst J, Deacon C . Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998; 47(11):1663-70. DOI: 10.2337/diabetes.47.11.1663. View

Schwarzer D, Finking R, Marahiel M . Nonribosomal peptides: from genes to products. Nat Prod Rep. 2003; 20(3):275-87. DOI: 10.1039/b111145k. View

Mentlein R . Dipeptidyl-peptidase IV (CD26)--role in the inactivation of regulatory peptides. Regul Pept. 1999; 85(1):9-24. DOI: 10.1016/s0167-0115(99)00089-0. View

Yasuda N, Yamazaki K, Inoue T, Nagakura T . [Therapeutic potential of DPP-IV inhibitor for the treatment of Type 2 diabetes]. Nihon Yakurigaku Zasshi. 2005; 125(6):379-84. DOI: 10.1254/fpj.125.379. View

Yasuda N, Nagakura T, Inoue T, Yamazaki K, Katsutani N, Takenaka O . E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor. Eur J Pharmacol. 2006; 548(1-3):181-7. DOI: 10.1016/j.ejphar.2006.08.011. View

Someya Y, Tahara A, Nakano R, Matsuyama-Yokono A, Nagase I, Fukunaga Y . Pharmacological profile of ASP8497, a novel, selective, and competitive dipeptidyl peptidase-IV inhibitor, in vitro and in vivo. Naunyn Schmiedebergs Arch Pharmacol. 2008; 377(3):209-17. DOI: 10.1007/s00210-008-0277-8. View

Bok J, Keller N . LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell. 2004; 3(2):527-35. PMC: 387652. DOI: 10.1128/EC.3.2.527-535.2004. View

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. DOI: 10.1016/S0076-6879(09)04808-3. View

Imamura K, Tsuyama Y, Hirata T . Identification and characterization of a novel fermented substance produced by edible Aspergillus oryzae AO-1 that inhibits DPP-IV activity. J Biosci Bioeng. 2010; 111(1):37-40. DOI: 10.1016/j.jbiosc.2010.08.013. View

10.

Chomczynski P . One-hour downward alkaline capillary transfer for blotting of DNA and RNA. Anal Biochem. 1992; 201(1):134-9. DOI: 10.1016/0003-2697(92)90185-a. View

11.

Watanabe K, Hotta K, Praseuth A, Koketsu K, Migita A, Boddy C . Total biosynthesis of antitumor nonribosomal peptides in Escherichia coli. Nat Chem Biol. 2006; 2(8):423-8. DOI: 10.1038/nchembio803. View

12.

Stachelhaus T, Schneider A, Marahiel M . Engineered biosynthesis of peptide antibiotics. Biochem Pharmacol. 1996; 52(2):177-86. DOI: 10.1016/0006-2952(96)00111-6. View

13.

Kobayashi T, Abe K, Asai K, Gomi K, Juvvadi P, Kato M . Genomics of Aspergillus oryzae. Biosci Biotechnol Biochem. 2007; 71(3):646-70. DOI: 10.1271/bbb.60550. View

14.

Machida M, Asai K, Sano M, Tanaka T, Kumagai T, Terai G . Genome sequencing and analysis of Aspergillus oryzae. Nature. 2005; 438(7071):1157-61. DOI: 10.1038/nature04300. View

15.

Ishi K, Watanabe T, Juvvadi P, Maruyama J, Kitamoto K . Development of a modified positive selection medium that allows to isolate Aspergillus oryzae strains cured of the integrated niaD-based plasmid. Biosci Biotechnol Biochem. 2005; 69(12):2463-5. DOI: 10.1271/bbb.69.2463. View

16.

Bacha N, Dao H, Atoui A, Mathieu F, OCallaghan J, Puel O . Cloning and characterization of novel methylsalicylic acid synthase gene involved in the biosynthesis of isoasperlactone and asperlactone in Aspergillus westerdijkiae. Fungal Genet Biol. 2009; 46(10):742-9. DOI: 10.1016/j.fgb.2009.07.002. View

17.

Walsh C . Combinatorial biosynthesis of antibiotics: challenges and opportunities. Chembiochem. 2002; 3(2-3):125-34. DOI: 10.1002/1439-7633(20020301)3:2/3<124::AID-CBIC124>3.0.CO;2-J. View

18.

Tokuoka M, Seshime Y, Fujii I, Kitamoto K, Takahashi T, Koyama Y . Identification of a novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) gene required for the biosynthesis of cyclopiazonic acid in Aspergillus oryzae. Fungal Genet Biol. 2008; 45(12):1608-15. DOI: 10.1016/j.fgb.2008.09.006. View

19.

Kiyota T, Hamada R, Sakamoto K, Iwashita K, Yamada O, Mikami S . Aflatoxin non-productivity of Aspergillus oryzae caused by loss of function in the aflJ gene product. J Biosci Bioeng. 2011; 111(5):512-7. DOI: 10.1016/j.jbiosc.2010.12.022. View

20.

Nagakura T, Yasuda N, Yamazaki K, Ikuta H, Tanaka I . Enteroinsular axis of db/db mice and efficacy of dipeptidyl peptidase IV inhibition. Metabolism. 2003; 52(1):81-6. DOI: 10.1053/meta.2003.50014. View