Sprusansky Ondrej, Stirrett Karen, Skinner Deborah, Denoya Claudio, Westpheling Janet
Genetics Department, University of Georgia, Athens, GA 30602, USA.
J Bacteriol. 2005 Jan;187(2):664-71. doi: 10.1128/JB.187.2.664-671.2005.
Products from the degradation of the branched-chain amino acids valine, leucine, and isoleucine contribute to the production of a number of important cellular metabolites, including branched-chain fatty acids, ATP and other energy production, cell-cell signaling for morphological development, and the synthesis of precursors for polyketide antibiotics. The first nonreversible reactions in the degradation of all three amino acids are catalyzed by the same branched-chain alpha-keto acid dehydrogenase (BCDH) complex. Actinomycetes are apparently unique among bacteria in that they contain two separate gene clusters, each of which encodes a BCDH enzyme complex. Here, we show that one of these clusters in Streptomyces coelicolor is regulated, at least in part, at the level of transcription by the product of the bkdR gene. The predicted product of this gene is a protein with similarity to a family of proteins that respond to leucine and serve to activate transcription of amino acid utilization operons. Unlike most other members of this class, however, the S. coelicolor bkdR gene product serves to repress transcription, suggesting that the branched-chain amino acids act as inducers rather than coactivators of transcription. BkdR likely responds to the presence of branched-chain amino acids. Its role in transcriptional regulation may be rationalized by the fact that transition from vegetative growth to aerial mycelium production, the first stage of morphological development in these complex bacteria, is coincident with extensive cellular lysis generating abundant amounts of protein that likely serve as the predominant source of carbon and nitrogen for metabolism. We suggest that bkdR plays a key role in the ability of Streptomyces species to sense nutrient availability and redirect metabolism for the utilization of branched-chain amino acids for energy, carbon, and perhaps even morphogen synthesis. A null mutant of bkdR is itself defective in morphogenesis and antibiotic production, suggesting that the role of the bkdR gene product may be more global than specific nutrient utilization.
支链氨基酸缬氨酸、亮氨酸和异亮氨酸降解产生的产物有助于多种重要细胞代谢物的生成，包括支链脂肪酸、ATP及其他能量产生、参与形态发育的细胞间信号传导，以及聚酮类抗生素前体的合成。这三种氨基酸降解过程中的首个不可逆反应均由同一支链α-酮酸脱氢酶（BCDH）复合体催化。放线菌在细菌中似乎独具特色，因为它们含有两个独立的基因簇，每个基因簇都编码一种BCDH酶复合体。在此，我们表明天蓝色链霉菌中的其中一个基因簇至少在转录水平上受到bkdR基因产物的调控。该基因的预测产物是一种蛋白质，与一类响应亮氨酸并激活氨基酸利用操纵子转录的蛋白质相似。然而，与该类别的大多数其他成员不同，天蓝色链霉菌的bkdR基因产物起到抑制转录的作用，这表明支链氨基酸作为转录的诱导物而非共激活剂。BkdR可能对支链氨基酸的存在作出反应。其在转录调控中的作用可以通过以下事实来解释：从营养生长向气生菌丝体产生的转变，即这些复杂细菌形态发育的第一阶段，与广泛的细胞裂解同时发生，产生大量蛋白质，这些蛋白质可能作为代谢中碳和氮的主要来源。我们认为bkdR在链霉菌感知营养可用性并重新调整代谢以利用支链氨基酸获取能量、碳甚至可能用于形态发生素合成的能力中起关键作用。bkdR的缺失突变体本身在形态发生和抗生素生产方面存在缺陷，这表明bkdR基因产物的作用可能比特定营养利用更为广泛。
