Identification of a Cyclase Gene Dictating the C-9 Stereochemistry of Anthracyclines from Streptomyces Nogalater

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2000 Jan 20

PMID 10639368

Citations 9

Authors

S Torkkell

T Kunnari

K Palmu

J Hakala

P Mantsala

K Ylihonko

Affiliations

Soon will be listed here.

Abstract

Nogalamycin is an anthracycline antibiotic produced by Streptomyces nogalater. Its aglycone has a unique stereochemistry (7S, 9S, 10R) compared to that of most other anthracyclines (7S, 9R, 10R). The gene snoaL, encoding a nogalonic acid methyl ester cyclase for nogalamycin, was used to generate nogalamycinone, demonstrating that the single cyclase dictates the C-9 stereochemistry of anthracyclines.

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References

Kantola J, Kunnari T, Hautala A, Hakala J, Ylihonko K, Mantsala P . Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp. Microbiology (Reading). 2000; 146 ( Pt 1):155-163. DOI: 10.1099/00221287-146-1-155. View

Lomovskaya N, Filippini S, Nastro C, Fonstein L, Gallo M, Colombo A . The Streptomyces peucetius dpsY and dnrX genes govern early and late steps of daunorubicin and doxorubicin biosynthesis. J Bacteriol. 1998; 180(9):2379-86. PMC: 107179. DOI: 10.1128/JB.180.9.2379-2386.1998. View

Bibb M, Janssen G, Ward J . Cloning and analysis of the promoter region of the erythromycin resistance gene (ermE) of Streptomyces erythraeus. Gene. 1985; 38(1-3):215-26. DOI: 10.1016/0378-1119(85)90220-3. View

Penco S, Vigevani A, Tosi C, Fusco R, Borghi D, ARCAMONE F . Conformational flexibility of ring A in a series of substituted anthracyclines: 1H-n.m.r. and quantum mechanical studies. Anticancer Drug Des. 1986; 1(2):161-5. View

Arora S . Molecular structure, stereochemistry and interactions of steffimycin B, and DNA binding anthracycline antibiotic. J Biomol Struct Dyn. 1985; 3(2):377-85. DOI: 10.1080/07391102.1985.10508424. View

Wright F, Bibb M . Codon usage in the G+C-rich Streptomyces genome. Gene. 1992; 113(1):55-65. DOI: 10.1016/0378-1119(92)90669-g. View

Ylihonko K, Hakala J, Niemi J, Lundell J, Mantsala P . Isolation and characterization of aclacinomycin A-non-producing Streptomyces galilaeus (ATCC 31615) mutants. Microbiology (Reading). 1994; 140 ( Pt 6):1359-65. DOI: 10.1099/00221287-140-6-1359. View

Dickens M, Ye J, Strohl W . Analysis of clustered genes encoding both early and late steps in daunomycin biosynthesis by Streptomyces sp. strain C5. J Bacteriol. 1995; 177(3):536-43. PMC: 176625. DOI: 10.1128/jb.177.3.536-543.1995. View

Niemi J, Mantsala P . Nucleotide sequences and expression of genes from Streptomyces purpurascens that cause the production of new anthracyclines in Streptomyces galilaeus. J Bacteriol. 1995; 177(10):2942-5. PMC: 176975. DOI: 10.1128/jb.177.10.2942-2945.1995. View

10.

Madduri K, Hutchinson C . Functional characterization and transcriptional analysis of a gene cluster governing early and late steps in daunorubicin biosynthesis in Streptomyces peucetius. J Bacteriol. 1995; 177(13):3879-84. PMC: 177111. DOI: 10.1128/jb.177.13.3879-3884.1995. View

11.

Dickens M, Ye J, Strohl W . Cloning, sequencing, and analysis of aklaviketone reductase from Streptomyces sp. strain C5. J Bacteriol. 1996; 178(11):3384-8. PMC: 178101. DOI: 10.1128/jb.178.11.3384-3388.1996. View

12.

Ylihonko K, Tuikkanen J, Jussila S, Cong L, Mantsala P . A gene cluster involved in nogalamycin biosynthesis from Streptomyces nogalater: sequence analysis and complementation of early-block mutations in the anthracycline pathway. Mol Gen Genet. 1996; 251(2):113-20. DOI: 10.1007/BF02172908. View

13.

Ylihonko K, Hakala J, Kunnari T, Mantsala P . Production of hybrid anthracycline antibiotics by heterologous expression of Streptomyces nogalater nogalamycin biosynthesis genes. Microbiology (Reading). 1996; 142 ( Pt 8):1965-72. DOI: 10.1099/13500872-142-8-1965. View

14.

Rajgarhia V, Strohl W . Minimal Streptomyces sp. strain C5 daunorubicin polyketide biosynthesis genes required for aklanonic acid biosynthesis. J Bacteriol. 1997; 179(8):2690-6. PMC: 179019. DOI: 10.1128/jb.179.8.2690-2696.1997. View

15.

Torkkell S, Ylihonko K, Hakala J, Skurnik M, Mantsala P . Characterization of Streptomyces nogalater genes encoding enzymes involved in glycosylation steps in nogalamycin biosynthesis. Mol Gen Genet. 1998; 256(2):203-9. DOI: 10.1007/s004380050562. View

16.

WILEY P, Kelly R, CARON E, Wiley V, Johnson J, MACKELLAR F . Structure of nogalamycin. J Am Chem Soc. 1977; 99(2):542-9. DOI: 10.1021/ja00444a038. View