Fang_2008_J.Bacteriol_190_6014

Reference

Title : Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics - Fang_2008_J.Bacteriol_190_6014
Author(s) : Fang J , Zhang Y , Huang L , Jia X , Zhang Q , Zhang X , Tang G , Liu W
Ref : Journal of Bacteriology , 190 :6014 , 2008
Abstract :

Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to Delta chlD3 and Delta chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity.

PubMedSearch : Fang_2008_J.Bacteriol_190_6014
PubMedID: 18586939
Gene_locus related to this paper: micch-b5l6l6

Related information

Gene_locus micch-b5l6l6
Gene_locus_frgt micch-b5l6l6    micch-b5l6n1

Citations formats

Fang J, Zhang Y, Huang L, Jia X, Zhang Q, Zhang X, Tang G, Liu W (2008)
Cloning and characterization of the tetrocarcin A gene cluster from Micromonospora chalcea NRRL 11289 reveals a highly conserved strategy for tetronate biosynthesis in spirotetronate antibiotics
Journal of Bacteriology 190 :6014

Fang J, Zhang Y, Huang L, Jia X, Zhang Q, Zhang X, Tang G, Liu W (2008)
Journal of Bacteriology 190 :6014