Genetic factors that influence moenomycin production in streptomycetes.
Moenomycin, a natural phosphoglycolipid product that has a long history of use in animal nutrition, is currently considered an attractive starting point for the development of novel antibiotics. We recently reconstituted the biosynthesis of this natural product in a heterologous host, Streptomyces lividans TK24, but production levels were too low to be useful. We have examined several other streptomycetes strains as hosts and have also explored the overexpression of two pleiotropic regulatory genes, afsS and relA, on moenomycin production. A moenomycin-resistant derivative of S. albus J1074 was found to give the highest titers of moenomycin, and production was improved by overexpressing relA. Partial duplication of the moe cluster 1 in S. ghanaensis also increased average moenomycin production. The results reported here suggest that rational manipulation of global regulators combined with increased moe gene dosage could be a useful technique for improvement of moenomycin biosynthesis.
Makitrynskyy
Roman
R
Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, Grushevskogo st. 4, L'viv 79005, Ukraine.
Rebets
Yuriy
Y
Ostash
Bohdan
B
Zaburannyi
Nestor
N
Rabyk
Mariia
M
Walker
Suzanne
S
Fedorenko
Victor
V
D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000302:isolation & purification; D001455:Bambermycins / Q000096:biosynthesis* / Q000302:isolation & purification; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D018628:Gene Dosage; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D008969:Molecular Sequence Data; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism; D048170:Streptomyces lividans / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001455:Bambermycins