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Antimicrobial Agents and Chemotherapy, June 2006, p. 1946-1952, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00016-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Analysis of the Loading and Hydroxylation Steps in Lankamycin Biosynthesis in Streptomyces rochei

Kenji Arakawa, Kazuya Kodama, Satoshi Tatsuno, Sayoko Ide, and Haruyasu Kinashi*

Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan

Received 6 January 2006/ Returned for modification 22 February 2006/ Accepted 21 March 2006

The biosynthetic gene cluster of lankamycin (LM), a 14-member macrolide antibiotic, is encoded on the 210-kb linear plasmid pSLA2-L in Streptomyces rochei 7434AN4. LM contains a 3-hydroxy-2-butyl group at the C-13 position, which is different from an ethyl group in erythromycin. The following two possibilities could be considered for the origin of this starter moiety of LM biosynthesis: (i) an extra module exists in the biosynthetic gene cluster and loads an additional acetate molecule, or (ii) 3-hydroxy-2-butyrate or its equivalent is loaded and incorporated as a starter. The former possibility was eliminated by the complete sequencing of pSLA2-L, which showed no extra module. On the other hand, the latter was confirmed by incorporation of deuterium in [3-2H]DL-isoleucine into the C-14 position of LM. The timing of hydroxylation reactions at the C-15 and C-8 positions of LM was studied by constructing disruptants of two P450 hydroxylase genes, lkmF (orf26) and lkmK (orf37). The lkmF disruptant produced 8-deoxylankamycin, while the lkmK disruptant produced both 15-deoxylankamycin and 8,15-dideoxylankamycin. These results clearly showed that LkmF is a C-8 hydroxylase and LkmK is a C-15 hydroxylase in LM biosynthesis and in addition suggested the order of hydroxylation steps; namely, hydroxylation may occur at first at C-15 by LkmK and then at C-8 by LkmF.

* Corresponding author. Mailing address: Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan. Phone: 81-82-424-7869. Fax: 81-82-424-7869. E-mail: kinashi{at}hiroshima-u.ac.jp.

Antimicrobial Agents and Chemotherapy, June 2006, p. 1946-1952, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00016-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Arakawa, K., Mochizuki, S., Yamada, K., Noma, T., Kinashi, H. (2007). {gamma}-Butyrolactone autoregulator-receptor system involved in lankacidin and lankamycin production and morphological differentiation in Streptomyces rochei. Microbiology 153: 1817-1827 [Abstract] [Full Text]  


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