TY - JOUR
T1 - Identification of the function of gene lndM2 encoding a bifunctional oxygenase-reductase involved in the biosynthesis of the antitumor antibiotic landomycin E by Streptomyces globisporus 1912 supports the originally assigned structure for landomycinone
AU - Zhu, Lili
AU - Ostash, Bohdan
AU - Rix, Uwe
AU - Nur-E-Alam, Mohammad
AU - Mayers, Almuth
AU - Luzhetskyy, Andriy
AU - Mendez, Carmen
AU - Salas, Jose A.
AU - Bechthold, Andreas
AU - Fedorenko, Victor
AU - Rohr, Jürgen
PY - 2005/1/21
Y1 - 2005/1/21
N2 - (Chemical Equation Presented) The angucycline antibiotic family of the landomycins displays potent antitumor activity. To elucidate early post polyketide synthase (PKS) tailoring steps of the landomycin E biosynthetic pathway in Streptomyces globisporus 1912, the mutant S. globisporus M12 was prepared through gene replacement experiment of lndM2. It encodes an enzyme with putative oxygenase and reductase domains, according to sequencing of the gene and its counterpart lanM2 from S. cyanogenus S136 landomycin A biosynthetic gene cluster. The isolation of the novel shunt products 11-hydroxytetrangomycin and 4-hydroxytetrangomycin along with the well-known angucyclines tetrangomycin and tetrangulol from the culture of S. globisporus M12 provides evidence for the involvement of lndM2 in the early biosynthetic pathway of the landomycins, in particular in the formation of the alicyclic 6-hydroxy function of the landomycin aglycon. We therefore propose LndM2 to be responsible for both hydroxylation of the 6-position and its subsequent reduction. These reactions are necessary before the glycosylation reactions can occur. The results are in agreement with the originally published structure of landomycin but do not support the recently suggested revised structure.
AB - (Chemical Equation Presented) The angucycline antibiotic family of the landomycins displays potent antitumor activity. To elucidate early post polyketide synthase (PKS) tailoring steps of the landomycin E biosynthetic pathway in Streptomyces globisporus 1912, the mutant S. globisporus M12 was prepared through gene replacement experiment of lndM2. It encodes an enzyme with putative oxygenase and reductase domains, according to sequencing of the gene and its counterpart lanM2 from S. cyanogenus S136 landomycin A biosynthetic gene cluster. The isolation of the novel shunt products 11-hydroxytetrangomycin and 4-hydroxytetrangomycin along with the well-known angucyclines tetrangomycin and tetrangulol from the culture of S. globisporus M12 provides evidence for the involvement of lndM2 in the early biosynthetic pathway of the landomycins, in particular in the formation of the alicyclic 6-hydroxy function of the landomycin aglycon. We therefore propose LndM2 to be responsible for both hydroxylation of the 6-position and its subsequent reduction. These reactions are necessary before the glycosylation reactions can occur. The results are in agreement with the originally published structure of landomycin but do not support the recently suggested revised structure.
UR - http://www.scopus.com/inward/record.url?scp=19944430903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=19944430903&partnerID=8YFLogxK
U2 - 10.1021/jo0483623
DO - 10.1021/jo0483623
M3 - Article
C2 - 15651811
AN - SCOPUS:19944430903
SN - 0022-3263
VL - 70
SP - 631
EP - 638
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 2
ER -