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2.A.78 The Branched Chain Amino Acid Exporter (LIV-E) Family

The LIV-E family consists of pairs of integral membane proteins. Functional data are available for AzlC and AzlD of Bacillus subtilis which together comprise an efflux pump for branched chain amino acids, leucine, isoleucine and valine. Overexpression of AzlC and AzlD (encoded within a single operon, the azlBCDEF operon) gives rise to resistance to 4-azaleucine. The azlE gene encodes a homologue of the BrnQ proteins of Lactobacillus delbrueckii and Corynebacterium glutamicum which are branched chain amino acid:H+ symport (uptake) permeases.

The homologous BrnE-BrnF system has been functionally characterized from Corynebacterium glutamicum (Kennerknecht et al., 2002; Trötschel et al., 2005). Both proteins were shown to be required for activity, and efflux of L-methionine, isoleucine, leucine and valine was demonstrated. These two proteins exhibit 7 and 4 putative TMSs, respectively. Limited evidence suggests that these proteins may have arisen from an unusual gene triplication event in which a 4 TMS-encoding element triplicated to give 8 and 4 TMS-encoding elements, and that the N-terminal TMS in the larger protein was lost to give a 7 TMS protein (Kennerknecht et al., 2002). The best inducer of brnFE operon expression is cytoplasmic L-methionine, suggesting that methionine is the native substrate.

Homologues of AzlC and AzlD are found in a diverse group of Gram-negative and Gram-positive bacteria as well as archaea. Several Gram-negative α-proteobacteria have 2 or 3 paralogues. Phylogenetic clustering of paralogues suggests that they are very divergent in sequence, resulting from early gene duplication events. It is therefore anticipated that they will not serve a unified function.

The generalized transport reaction presumed to be catalyzed by members of the LIV-E family is:

L, I or V (in) nH+ (out) → L, I or V (out) nH+ (in)

References associated with 2.A.78 family:

Belitsky, B.R., M.C.U. Gustafsson, A.L. Sonenshein, and C. von Wachenfeldt. (1997). An lrp-like gene of Bacillus subtilis involved in branched-chain amino acid transport. J. Bacteriol. 179: 5448-5457. 9287000
Kennerknecht, N., H. Sahm, M.R. Yen, M. Patek, M.H. Saier, Jr., and L. Eggeling. (2002). Export of L-isoleucine from Corynebacterium glutamicum: a two-gene-encoded member of a new translocator family. J. Bacteriol. 184: 3947-3956. 12081967
Trötschel, C., D. Deutenberg, B. Bathe, A. Burkovski, and R. Krämer. (2005). Characterization of methionine export in Corynebacterium glutamicum. J. Bacteriol. 187: 3786-3794. 15901702
Xiao, J., D. Wang, L. Wang, Y. Jiang, L. Xue, S. Sui, J. Wang, C. Guo, R. Wang, J. Wang, N. Li, H. Fan, and M. Lv. (2020). Increasing L-lysine production in Corynebacterium glutamicum by engineering amino acid transporters. Amino Acids 52: 1363-1374. 33021685