Otzen Marleen, Crismaru Ciprian G, Postema Christiaan P, Wijma Hein J, Heberling Matthew M, Szymanski Wiktor, de Wildeman Stefaan, Janssen Dick B
Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
DSM Pharmaceutical Products, Geleen, The Netherlands.
Appl Microbiol Biotechnol. 2015 Nov;99(21):8987-98. doi: 10.1007/s00253-015-6551-z. Epub 2015 May 26.
Pseudomonas species strain SBV1 can rapidly grow on medium containing β-valine as a sole nitrogen source. The tertiary amine feature of β-valine prevents direct deamination reactions catalyzed by aminotransferases, amino acid dehydrogenases, and amino acid oxidases. However, lyase- or aminomutase-mediated conversions would be possible. To identify enzymes involved in the degradation of β-valine, a PsSBV1 gene library was prepared and used to complement the β-valine growth deficiency of a closely related Pseudomonas strain. This resulted in the identification of a gene encoding β-valinyl-coenzyme A ligase (BvaA) and two genes encoding β-valinyl-CoA ammonia lyases (BvaB1 and BvaB2). The BvaA protein demonstrated high sequence identity to several known phenylacetate CoA ligases. Purified BvaA enzyme did not convert phenyl acetic acid but was able to activate β-valine in an adenosine triphosphate (ATP)- and CoA-dependent manner. The substrate range of the enzyme appears to be narrow, converting only β-valine and to a lesser extent, 3-aminobutyrate and β-alanine. Characterization of BvaB1 and BvaB2 revealed that both enzymes were able to deaminate β-valinyl-CoA to produce 3-methylcrotonyl-CoA, a common intermediate in the leucine degradation pathway. Interestingly, BvaB1 and BvaB2 demonstrated no significant sequence identity to known CoA-dependent ammonia lyases, suggesting they belong to a new family of enzymes. BLAST searches revealed that BvaB1 and BvaB2 show high sequence identity to each other and to several enoyl-CoA hydratases, a class of enzymes that catalyze a similar reaction with water instead of amine as the leaving group.
假单胞菌属菌株SBV1能够在以β-缬氨酸作为唯一氮源的培养基上快速生长。β-缬氨酸的叔胺特性可防止由转氨酶、氨基酸脱氢酶和氨基酸氧化酶催化的直接脱氨反应。然而,裂解酶或氨基变位酶介导的转化是可能的。为了鉴定参与β-缬氨酸降解的酶,制备了PsSBV1基因文库,并用于补充密切相关的假单胞菌菌株的β-缬氨酸生长缺陷。这导致鉴定出一个编码β-缬氨酰辅酶A连接酶(BvaA)的基因和两个编码β-缬氨酰辅酶A氨裂解酶(BvaB1和BvaB2)的基因。BvaA蛋白与几种已知的苯乙酸辅酶A连接酶具有高度的序列同一性。纯化的BvaA酶不能转化苯乙酸,但能够以三磷酸腺苷(ATP)和辅酶A依赖性方式激活β-缬氨酸。该酶的底物范围似乎较窄,仅转化β-缬氨酸,在较小程度上转化3-氨基丁酸和β-丙氨酸。对BvaB1和BvaB2的表征表明,这两种酶都能够使β-缬氨酰辅酶A脱氨,生成3-甲基巴豆酰辅酶A,这是亮氨酸降解途径中的一个常见中间体。有趣的是,BvaB1和BvaB2与已知的辅酶A依赖性氨裂解酶没有显著的序列同一性,这表明它们属于一个新的酶家族。BLAST搜索显示,BvaB1和BvaB2彼此之间以及与几种烯酰辅酶A水合酶具有高度的序列同一性,烯酰辅酶A水合酶是一类催化类似反应的酶,反应中离去基团是水而非胺。