Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions.
The biosynthetic gene cluster for the angiogenesis inhibitor borrelidin has been cloned from Streptomyces parvulus Tü4055. Sequence analysis indicates that the macrolide ring of borrelidin is formed by a modular polyketide synthase (PKS) (borA1-A6), a result that was confirmed by disruption of borA3. The borrelidin PKS is striking because only seven rather than the nine modules expected for a nonaketide product are encoded by borA1-A6. The starter unit of the PKS has been verified as trans-cyclopentane-1,2-dicarboxylic acid (trans-1,2-CPDA), and the genes involved in its biosynthesis identified. Other genes responsible for biosynthesis of the nitrile moiety, regulation, and self-resistance were also identified.
Olano
Carlos
C
Departamento de Biologá Funcional e Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
Wilkinson
Barrie
B
Sánchez
César
C
Moss
Steven J
SJ
Sheridan
Rose
R
Math
Vidya
V
Weston
Alison J
AJ
Braña
Alfredo F
AF
Martin
Christine J
CJ
Oliynyk
Markiyan
M
Méndez
Carmen
C
Leadlay
Peter F
PF
Salas
José A
JA
D020533:Angiogenesis Inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D003001:Cloning, Molecular; D003517:Cyclopentanes / Q000138:chemical synthesis; D003998:Dicarboxylic Acids / Q000138:chemical synthesis; D005233:Fatty Alcohols / Q000737:chemistry / Q000378:metabolism*; D005798:Genes, Bacterial; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics; D005810:Multigene Family; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D003517:Cyclopentanes; D003998:Dicarboxylic Acids; D005233:Fatty Alcohols; D009097:Multienzyme Complexes; C005066:borrelidin