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Journal of Bacteriology, July 2006, p. 5113-5123, Vol. 188, No. 14
0021-9193/06/$08.00+0     doi:10.1128/JB.01919-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Occurrence of Two 5-Aminolevulinate Biosynthetic Pathways in Streptomyces nodosus subsp. asukaensis Is Linked with the Production of Asukamycin

Miroslav Petrícek,1* Katerina Petrícková,1 Libor Havlícek,2 and Jürgen Felsberg1

Institute of Microbiology AS CR,1 Institute of Experimental Botany AS CR, Vídenská 1083, 142 20 Prague 4, Czech Republic2

Received 15 December 2005/ Accepted 25 April 2006

We report the results of cloning genes for two key biosynthetic enzymes of different 5-aminolevulinic acid (ALA) biosynthetic routes from Streptomyces. The genes encode the glutamyl-tRNAGlu reductase (GluTR) of the C5 pathway and the ALA synthase (ALAS) of the Shemin pathway. While Streptomyces coelicolor A3(2) synthesizes ALA via the C5 route, both pathways are operational in Streptomyces nodosus subsp. asukaensis, a producer of asukamycin. In this strain, the C5 route produces ALA for tetrapyrrole biosynthesis; the ALA formed by the Shemin pathway serves as a precursor of the 2-amino-3-hydroxycyclopent-2-enone moiety (C5N unit), an antibiotic component. The growth of S. nodosus and S. coelicolor strains deficient in the GluTR genes (gtr) is strictly dependent on ALA or heme supplementation, whereas the defect in the ALAS-encoding gene (hemA-asuA) abolishes the asukamycin production in S. nodosus. The recombinant hemA-asuA gene was expressed in Escherichia coli and in Streptomyces, and the encoded enzyme activity was demonstrated both in vivo and in vitro. The hemA-asuA gene is situated within a putative cluster of asukamycin biosynthetic genes. This is the first report about the cloning of genes for two different ALA biosynthetic routes from a single bacterium.

* Corresponding author. Mailing address: Institute of Microbiology AS CR, Vídenská 1083, 142 20 Prague 4, Czech Republic. Phone: 420 24106 2426. Fax: 420 24106 2347. E-mail: petras{at}biomed.cas.cz.

Journal of Bacteriology, July 2006, p. 5113-5123, Vol. 188, No. 14
0021-9193/06/$08.00+0     doi:10.1128/JB.01919-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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