Finely Tuned Regulation of the Aromatic Amine Degradation Pathway in Escherichia coli

Abstract

FeaR is an AraC family regulator that activates transcription of the tynA and feaB genes in Escherichia coli. TynA is a periplasmic topaquinone-and copper-containing amine oxidase, and FeaB is a cytosolic NAD-linked aldehyde dehydrogenase. Phenylethylamine, tyramine, and dopamine are oxidized by TynA to the corresponding aldehydes, releasing one equivalent of H 2 O 2 and NH 3 . The aldehydes can be oxidized to carboxylic acids by FeaB, and (in the case of phenylacetate) can be further degraded to enter central metabolism. Thus, phenylethylamine can be used as a carbon and nitrogen source, while tyramine and dopamine can be used only as sources of nitrogen. Using genetic, biochemical and computational approaches, we show that the FeaR binding site is a TGNCA-N 8 -AAA motif that occurs in 2 copies in the tynA and feaB promoters. We show that the coactivator for FeaR is the product rather than the substrate of the TynA reaction. The feaR gene is upregulated by carbon or nitrogen limitation, which we propose reflects regulation of feaR by the cyclic AMP receptor protein (CRP) and the nitrogen assimilation control protein (NAC), respectively. In carbon-limited cells grown in the presence of a TynA substrate, tynA and feaB are induced, whereas in nitrogen-limited cells, only the tynA promoter is induced. We propose that tynA and feaB expression is finely tuned to provide the FeaB activity that is required for carbon source utilization and the TynA activity required for nitrogen and carbon source utilization.

Conversion of Norepinephrine to 3,4-Dihdroxymandelic Acid in Escherichia coli Requires the QseBC Quorum-Sensing System and the FeaR Transcription Factor

“…The first step is carried out by a primary amine oxidase, TynA, which produces the intermediate 3,4-dihydroxyphenylglycol-aldehyde (DOPEGAL), and the second step is catalyzed by an aromatic aldehyde dehydrogenase, FeaB (22). TynA and FeaB are also produced by other enteric bacteria, where their characterized function is the utilization of aromatic amines as nitrogen sources and, in at least one case, as a carbon source (23). The expression of TynA and FeaB in E. coli CV1 requires prior exposure to NE and subsequent protein synthesis, and the induction of tynA and feaB transcription depends upon the presence of the histidine protein kinase QseC (17).…”

“…FeaR is a transcriptional regulator of the AraC family (23) and has been characterized as an essential transcription factor for the expression of tynA and feaB in response to exposure to aromatic amines. The feaR, feaB, and tynA genes are adjacent but are divergently transcribed (23). The feaB and tynA genes have separate promoters and are somewhat differently regulated, although both promoters have two well-defined, tandem FeaR-binding sites upstream of the Ϫ35 region of their respective promoters (23).…”

Two Different Quinohemoprotein Amine Dehydrogenases Initiate Anaerobic Degradation of Aromatic Amines in Aromatoleum aromaticum EbN1

“…Although the aerobic degradation of aromatic amines has been described for a number of bacteria (36)(37)(38)(39), no experimental evidence has been available for their conversion under anoxic conditions. Genome analysis of A. aromaticum EbN1 and Azoarcus sp.…”

Quorum‐dependent transfer of the opine‐catabolic plasmid pAoF64/95 is regulated by a novel mechanism involving inhibition of the TraR antiactivator TraM

“…That a metabolic intermediate is the true inducer is uncommon but not unique. For example, allolactose, a metabolic product of lactose is the true ligand for LacI (Burstein, Cohn, Kepes, & Monod, ; Jobe & Bourgeois, ), while tyramine, a catabolic intermediate in the conversion of phenylethylamine to phenylacetate, is the ligand recognized by FeaR, the AraC‐like activator that regulates the pathway in Escherichia coli (Zeng & Spiro, ). More relevant to this system, arabinose‐2‐phosphate, the first intermediate in catabolism of agrocinopines A and B, is the ligand recognized and bound by AccR, the FucR‐like repressor that controls expression of the acc operon as well as traR in the arc operon of pTiC58 (El Sahili et al., ).…”

“…Discs impregnated with mannitol (MAN), MOP, or DFG were placed on the streaks all as described in Experimental Procedures That a metabolic intermediate is the true inducer is uncommon but not unique. For example, allolactose, a metabolic product of lactose is the true ligand for LacI (Burstein, Cohn, Kepes, & Monod, 1965;Jobe & Bourgeois, 1972), while tyramine, a catabolic intermediate in the conversion of phenylethylamine to phenylacetate, is the ligand recognized by FeaR, the AraC-like activator that regulates the pathway in Escherichia coli (Zeng & Spiro, 2013). RepABC plasmids with Class I QS-regulated conjugative transfer systems fall into two organizational types, Group I and Group II (Wetzel et al, 2015).…”