Kyoto University, Sakyo-ku, Japan.
Appl Microbiol Biotechnol. 2011 Feb;89(3):739-46. doi: 10.1007/s00253-010-2924-5. Epub 2010 Oct 16.
NADP(+)-dependent aminoalcohol dehydrogenase (AADH) of Rhodococcus erythropolis MAK154 catalyzes the reduction of (S)-1-phenyl-1-keto-2-methylaminopropane ((S)-MAK) to d-pseudoephedrine, which is used as a pharmaceutical. AADH is suggested to participate in aminoalcohol or aminoketone metabolism in this organism because it is induced by the addition of several aminoalcohols, such as 1-amino-2-propanol. Genetic analysis of around the aadh gene showed that some open reading frames (ORFs) are involved in this metabolic pathway. Four of these ORFs might form a carboxysome-like polyhedral organelle, and others are predicted to encode aminotransferase, aldehyde dehydrogenase, phosphotransferase, and regulator protein. OrfE, a homologous ORF of the FadR subfamily of GntR transcriptional regulators, lies downstream from aadh. To investigate whether or not orfE plays a role in the regulation of aadh expression, the gene disruption mutant of R. erythropolis MAK154 was constructed. The ΔorfE strain showed higher AADH activity than wild-type strain. In addition, a transformed strain, which harbored multi-orfE, showed no AADH activity even in the induced condition with 1-amino-2-propanol. These results suggest that OrfE is a negative regulator that represses aadh expression in the absence of 1-amino-2-propanol.
红平红球菌 MAK154 中的烟酰胺腺嘌呤二核苷酸(NADP(+))-依赖性氨基醇脱氢酶(AADH)可催化(S)-1-苯基-1-酮-2-甲基氨基丙烷((S)-MAK)还原为 d-伪麻黄碱,后者被用作药物。由于 AADH 可被几种氨基醇(如 1-氨基-2-丙醇)的添加诱导,因此它被认为参与该生物体中的氨基醇或氨基酮代谢。围绕 aadh 基因的遗传分析表明,一些开放阅读框(ORF)参与了该代谢途径。其中四个 ORF 可能形成类似于羧酶体的多面状细胞器,而其他 ORF 则预测编码氨基转移酶、醛脱氢酶、磷酸转移酶和调节蛋白。OrfE 是 GntR 转录调节因子 FadR 亚家族的同源 ORF,位于 aadh 的下游。为了研究 orfE 是否在调节 aadh 表达中起作用,构建了红平红球菌 MAK154 的基因缺失突变体。与野生型菌株相比,ΔorfE 菌株的 AADH 活性更高。此外,即使在添加 1-氨基-2-丙醇的诱导条件下,携带多orfE 的转化菌株也没有 AADH 活性。这些结果表明,OrfE 是一种负调控因子,在没有 1-氨基-2-丙醇的情况下抑制 aadh 表达。