Identification of a Biosynthetic Gene Cluster Responsible for the Production of a New Pyrrolopyrimidine Natural Product-Huimycin

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2020 Jul 26

PMID 32708402

Citations 8

Authors

Hui Shuai

Maksym Myronovskyi

Suvd Nadmid

Andriy Luzhetskyy

Affiliations

Soon will be listed here.

Abstract

Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper.

Citing Articles

Unlocking the Potential of Pyrrole: Recent Advances in New Pyrrole-Containing Compounds with Antibacterial Potential.

Rusu A, Oancea O, Tanase C, Uncu L Int J Mol Sci. 2024; 25(23.

PMID: 39684580 PMC: 11640851. DOI: 10.3390/ijms252312873.

Biosynthesis and function of 7-deazaguanine derivatives in bacteria and phages.

de Crecy-Lagard V, Hutinet G, Cediel-Becerra J, Yuan Y, Zallot R, Chevrette M Microbiol Mol Biol Rev. 2024; 88(1):e0019923.

PMID: 38421302 PMC: 10966956. DOI: 10.1128/mmbr.00199-23.

Bacterial natural product discovery by heterologous expression.

Kadjo A, Eustaquio A J Ind Microbiol Biotechnol. 2023; 50(1).

PMID: 38052428 PMC: 10727000. DOI: 10.1093/jimb/kuad044.

Bioactive Metabolites from Terrestrial and Marine Actinomycetes.

Ngamcharungchit C, Chaimusik N, Panbangred W, Euanorasetr J, Intra B Molecules. 2023; 28(15).

PMID: 37570885 PMC: 10421486. DOI: 10.3390/molecules28155915.

Properties of Multidrug-Resistant Mutants Derived from Heterologous Expression Chassis Strain J1074.

Dolya B, Hryhorieva O, Sorochynska K, Lopatniuk M, Ostash I, Tseduliak V Microorganisms. 2023; 11(5).

PMID: 37317150 PMC: 10220713. DOI: 10.3390/microorganisms11051176.

References

McCarty R, Bandarian V . Deciphering deazapurine biosynthesis: pathway for pyrrolopyrimidine nucleosides toyocamycin and sangivamycin. Chem Biol. 2008; 15(8):790-8. PMC: 2603307. DOI: 10.1016/j.chembiol.2008.07.012. View

Iijima M, Kubota Y, Sawa R, Kubota Y, Hatano M, Igarashi M . A guanine derivative as a new MEK inhibitor produced by Streptomyces sp. MK63-43F2. J Antibiot (Tokyo). 2017; . DOI: 10.1038/ja.2017.100. View

Suhadolnik R, Uematsu T, Uematsu H . Toyocamycin: phosphorylation and incorporation into RNA and DNA and the biochemical properties of the triphosphate. Biochim Biophys Acta. 1967; 149(1):41-9. DOI: 10.1016/0005-2787(67)90689-2. View

Lindberg B, KLENOW H, Hansen K . Some properties of partially purified mammalian adenosine kinase. J Biol Chem. 1967; 242(3):350-6. View

Rebets Y, Tokovenko B, Lushchyk I, Ruckert C, Zaburannyi N, Bechthold A . Complete genome sequence of producer of the glycopeptide antibiotic Aculeximycin Kutzneria albida DSM 43870T, a representative of minor genus of Pseudonocardiaceae. BMC Genomics. 2014; 15:885. PMC: 4210621. DOI: 10.1186/1471-2164-15-885. View

Anzai K, Nakamura G, Suzuki S . A new antibiotic, tubercidin. J Antibiot (Tokyo). 1957; 10(5):201-4. View

Urbonavicius J, Qian Q, Durand J, Hagervall T, Bjork G . Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J. 2001; 20(17):4863-73. PMC: 125605. DOI: 10.1093/emboj/20.17.4863. View

Harada F, Nishimura S . Possible anticodon sequences of tRNA His , tRNA Asm , and tRNA Asp from Escherichia coli B. Universal presence of nucleoside Q in the first postion of the anticondons of these transfer ribonucleic acids. Biochemistry. 1972; 11(2):301-8. DOI: 10.1021/bi00752a024. View

McCarty R, Bandarian V . Biosynthesis of pyrrolopyrimidines. Bioorg Chem. 2012; 43:15-25. PMC: 4022189. DOI: 10.1016/j.bioorg.2012.01.001. View

10.

Blin K, Shaw S, Steinke K, Villebro R, Ziemert N, Lee S . antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline. Nucleic Acids Res. 2019; 47(W1):W81-W87. PMC: 6602434. DOI: 10.1093/nar/gkz310. View

11.

Roskoski Jr R . Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res. 2019; 144:19-50. DOI: 10.1016/j.phrs.2019.03.006. View

12.

Mogul A, Corsi K, McAuliffe L . Baricitinib: The Second FDA-Approved JAK Inhibitor for the Treatment of Rheumatoid Arthritis. Ann Pharmacother. 2019; 53(9):947-953. DOI: 10.1177/1060028019839650. View

13.

Loomis C, Bell R . Sangivamycin, a nucleoside analogue, is a potent inhibitor of protein kinase C. J Biol Chem. 1988; 263(4):1682-92. View

14.

Osada H, Sonoda T, Tsunoda K, Isono K . A new biological role of sangivamycin; inhibition of protein kinases. J Antibiot (Tokyo). 1989; 42(1):102-6. DOI: 10.7164/antibiotics.42.102. View

15.

Nishimura H, Katagiri K, Sato K, MAYAMA M, SHIMAOKA N . Toyocamycin, a new anti-candida antibiotics. J Antibiot (Tokyo). 1956; 9(2):60-2. View

16.

Rodriguez Estevez M, Myronovskyi M, Gummerlich N, Nadmid S, Luzhetskyy A . Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain subsp. NRRL B-24108. Mar Drugs. 2018; 16(11). PMC: 6265801. DOI: 10.3390/md16110435. View

17.

Rao K . Structure of sangivamycin. J Med Chem. 1968; 11(5):939-41. DOI: 10.1021/jm00311a005. View

18.

Uretsky S, Acs G, Reich E, Mori M, ALTWERGER L . Pyrrolopyrimidine nucleotides and protein synthesis. J Biol Chem. 1968; 243(2):306-12. View

19.

Kilpatrick M, Walker R . The nucleotide sequence of the tRNAMMet from the archaebacterium Thermoplasma acidophilum. Nucleic Acids Res. 1981; 9(17):4387-90. PMC: 327441. DOI: 10.1093/nar/9.17.4387. View

20.

Xu J, Song Z, Xu X, Ma Z, Bechthold A, Yu X . ToyA, a positive pathway-specific regulator for toyocamycin biosynthesis in Streptomyces diastatochromogenes 1628. Appl Microbiol Biotechnol. 2019; 103(17):7071-7084. DOI: 10.1007/s00253-019-09959-w. View