Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus.
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.
Ostash
Bohdan
B
Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, Grushevskyy st. 4, L'viv 79005, Ukraine.
Rix
Uwe
U
Rix
Lily L Remsing
LL
Liu
Tao
T
Lombo
Felipe
F
Luzhetskyy
Andriy
A
Gromyko
Oleksandr
O
Wang
Chenchen
C
Braña
Alfredo F
AF
Méndez
Carmen
C
Salas
José A
JA
Fedorenko
Victor
V
Rohr
Jürgen
J
D000617:Aminoglycosides / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D016695:Glycosyltransferases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010088:Oxidoreductases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000617:Aminoglycosides; D000970:Antineoplastic Agents; C493499:landomycin D; C113593:landomycin E; C493498:landomycin F; C493497:landomycin G; C493496:landomycin H; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D016695:Glycosyltransferases