Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions

Carlos Olano; Barrie Wilkinson; César Sánchez; Steven J Moss; Rose Sheridan; Vidya Math; Alison J Weston; Alfredo F Braña; Christine J Martin; Markiyan Oliynyk; Carmen Méndez; Peter F Leadlay; José A Salas

doi:10.1016/j.chembiol.2003.12.018

Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions

Chem Biol. 2004 Jan;11(1):87-97. doi: 10.1016/j.chembiol.2003.12.018.

Authors

Carlos Olano¹, Barrie Wilkinson, César Sánchez, Steven J Moss, Rose Sheridan, Vidya Math, Alison J Weston, Alfredo F Braña, Christine J Martin, Markiyan Oliynyk, Carmen Méndez, Peter F Leadlay, José A Salas

Affiliation

¹ Departamento de Biologá Funcional e Instituto Universitario de Oncologia del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.

PMID: 15112998
DOI: 10.1016/j.chembiol.2003.12.018

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / biosynthesis*
Angiogenesis Inhibitors / chemistry
Cloning, Molecular
Cyclopentanes / chemical synthesis
Dicarboxylic Acids / chemical synthesis
Fatty Alcohols / chemistry
Fatty Alcohols / metabolism*
Genes, Bacterial*
Models, Chemical
Molecular Sequence Data
Molecular Structure
Multienzyme Complexes / genetics
Multigene Family*
Sequence Analysis, DNA
Streptomyces / enzymology
Streptomyces / genetics*
Streptomyces / metabolism

Substances

Angiogenesis Inhibitors
Cyclopentanes
Dicarboxylic Acids
Fatty Alcohols
Multienzyme Complexes
borrelidin

Associated data

GENBANK/AB070949
GENBANK/AF237573
GENBANK/AJ002571
GENBANK/AJ580915
GENBANK/AY045929