Genetic organization of the putative salbostatin biosynthetic gene cluster including the 2-epi-5-epi-valiolone synthase gene in Streptomyces albus ATCC 21838.
The cyclization of sedoheptulose 7-phosphate to 2-epi-5-epi-valiolone, catalyzed by the 2-epi-5-epi-valiolone synthases, is the first committed step in the biosynthesis of C( 7 )N-aminocyclitol-containing natural products, such as validamycin and acarbose. These natural products contain in their structures a valienamine unit, which is important for their biological activity. The same core unit is also found in salbostatin, a related pseudodisaccharide that has strong trehalase inhibitory activity. In silico analysis of the putative biosynthetic gene cluster of salbostatin from Streptomyces albus ATCC 21838 revealed 20 open reading frames, including an acbC homolog gene (salQ), which is believed to be involved in the biosynthesis of salbostatin. The salQ gene was overexpressed in Escherichia coli and the catalytic function of the recombinant protein was confirmed to be a 2-epi-5-epi-valiolone synthase. In addition, SalF, SalL, SalM, SalN, SalO, and SalR were found to be homologous to AcbR, AcbM, AcbL, AcbN, AcbO, and AcbP from the acarbose pathway, respectively, which suggests that the biosynthesis of C(7)N-aminocyclitol moiety of salbostatin may be very similar to that of acarbose.
Choi
Woo Sik
WS
Department of Biological Science and Institute of Bioscience and Biotechnology, Myongji University, Yongin, 449-728, South Korea.
Wu
Xiumei
X
Choeng
Yong-Hoon
YH
Mahmud
Taifo
T
Jeong
Byeong Chul
BC
Lee
Sang Hee
SH
Chang
Yong Keun
YK
Kim
Chang-Joon
CJ
Hong
Soon-Kwang
SK
D020909:Acarbose / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D053138:Cyclohexenes / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006595:Hexosamines / Q000378:metabolism*; D008969:Molecular Sequence Data; D005810:Multigene Family; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics*
D001426:Bacterial Proteins; D053138:Cyclohexenes; D006595:Hexosamines; D011993:Recombinant Fusion Proteins; C532922:salbostatin; D020909:Acarbose