1887

Abstract

Tautomycetin (TMC) is a novel activated T-cell-specific immunosuppressive compound with a unique structure, containing an ester bond linkage between a terminal cyclic anhydride moiety and a linear polyketide chain bearing an unusual terminal alkene. A 3 kb gene, , with a deduced product of 1029 amino acid residues, located on the 3′-terminus of an approximately 70 kb contiguous TMC biosynthetic gene cluster, was found to have amino acid sequence homology with bacterial regulatory proteins. database comparisons revealed that TmcN belongs to the large ATP-binding regulators of the LuxR protein family. Gene disruption of from the sp. CK4412 chromosome resulted in significantly reduced antifungal activity against , as well as the absence of TMC. In addition, complementation by an integrative plasmid carrying restored TMC biosynthesis, strongly suggesting that TmcN is a positive regulator of TMC biosynthesis. Gene expression analysis by RT-PCR of the TMC biosynthetic genes revealed that a TmcN mutant strain exhibited reduced expression levels for most of the biosynthetic genes except for its own . It is thus suggested that TmcN is a pathway-specific positive regulator that activates transcription of the TMC biosynthetic pathway genes in sp. CK4412.

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2008-10-01
2019-10-18
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