Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tu4055:: Cluster analysis and assignment of functions

被引:136
作者
Olano, C
Wilkinson, B
Sánchez, C
Moss, SJ
Sheridan, R
Math, V
Weston, AJ
Braña, AF
Martin, CJ
Oliynyk, M
Méndez, C
Leadlay, PF
Salas, JA [1 ]
机构
[1] Univ Oviedo, Dept Biol Func, E-33006 Oviedo, Spain
[2] Univ Oviedo, IUOPA, E-33006 Oviedo, Spain
[3] Biot Technol Ltd, Little Chesterford CB10 1XL, Essex, England
[4] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
来源
CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 01期
关键词
D O I
10.1016/j.chembiol.2003.12.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The biosynthetic gene cluster for the angiogenesis inhibitor borrelidin has been cloned from Streptomyces parvulus Tu4055. 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.
引用
收藏
页码:87 / 97
页数:11
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