Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus |
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Authors: | Ostash Bohdan Rix Uwe Rix Lily L Remsing Liu Tao Lombo Felipe Luzhetskyy Andriy Gromyko Oleksandr Wang Chenchen Braña Alfredo F Méndez Carmen Salas José A Fedorenko Victor Rohr Jürgen |
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Institution: | Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, Grushevskyy st. 4, L'viv 79005, Ukraine. |
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Abstract: | A 3 kb DNA fragment from the Streptomyces globisporus 1912 landomycin E (LaE) biosynthetic gene cluster (lnd) was completely sequenced. Three open reading frames were identified, lndGT4, lndZ4, and lndZ5, whose probable translation products resemble a glycosyltransferase, a reductase, and a hydroxylase, respectively. Studies of generated mutants from disruption and complementation experiments involving the lndGT4 gene allowed us to determine that LndGT4 controls the terminal L-rhodinose sugar attachment during LaE biosynthesis and that LndZ4/LndZ5 are responsible for the unique C11-hydroxylation of the landomycins. Generation of the novel landomycins F, G, and H in the course of these studies provided evidence for the flexibility of lnd glycosyltransferases toward their acceptor substrates and a basis for initial structure-activity relationships within the landomycin family of antibiotics. |
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