Author/Authors :
Carlos Olano، نويسنده , , Barrie Wilkinson، نويسنده , , César S?nchez، نويسنده , , Steven J Moss، نويسنده , , Rose Sheridan، نويسنده , , Vidya Math، نويسنده , , Alison J Weston، نويسنده , , Alfredo F Bra?a، نويسنده , , Christine Saint-Martin، نويسنده , , Markiyan Oliynyk، نويسنده , , Carmen Méndez، نويسنده , , Peter F Leadlay، نويسنده , , José A Salas، نويسنده ,
Abstract :
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.
