溴仿生物合成的遗传和生化重建为海藻活性氧酶学提供了新见解。
Genetic and Biochemical Reconstitution of Bromoform Biosynthesis in Lends Insights into Seaweed Reactive Oxygen Species Enzymology.
机构信息
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
出版信息
ACS Chem Biol. 2020 Jun 19;15(6):1662-1670. doi: 10.1021/acschembio.0c00299. Epub 2020 Jun 8.
Marine macroalgae, seaweeds, are exceptionally prolific producers of halogenated natural products. Biosynthesis of halogenated molecules in seaweeds is inextricably linked to reactive oxygen species (ROS) signaling as hydrogen peroxide serves as a substrate for haloperoxidase enzymes that participate in the construction these halogenated molecules. Here, using red macroalga , a prolific producer of the ozone depleting molecule bromoform, we provide the discovery and biochemical characterization of a ROS-producing NAD(P)H oxidase from seaweeds. This discovery was enabled by our sequencing of genomes, in which we find the gene encoding the ROS-producing enzyme to be clustered with genes encoding bromoform-producing haloperoxidases. Biochemical reconstitution of haloperoxidase activities establishes that fatty acid biosynthesis can provide viable hydrocarbon substrates for bromoform production. The ROS production haloperoxidase enzymology that we describe here advances seaweed biology and biochemistry by providing the molecular basis for decades worth of physiological observations in ROS and halogenated natural product biosyntheses.
海洋大型藻类,即海藻,是卤代天然产物的特别丰富的生产者。海藻中卤代分子的生物合成与活性氧(ROS)信号密不可分,因为过氧化氢是参与构建这些卤代分子的卤过氧化物酶的底物。在这里,我们使用红海藻,一种臭氧消耗分子溴仿的丰富生产者,提供了一种从海藻中产生 ROS 的 NAD(P)H 氧化酶的发现和生化特征。这一发现得益于我们对基因组的测序,在测序中我们发现编码产生 ROS 的酶的基因与编码产生溴仿的卤过氧化物酶的基因簇在一起。卤过氧化物酶活性的生化重建确立了脂肪酸生物合成可以为溴仿的产生提供可行的碳氢化合物底物。我们在这里描述的 ROS 产生卤过氧化物酶酶学通过为 ROS 和卤代天然产物生物合成中数十年来的生理观察提供分子基础,推进了海藻生物学和生物化学的发展。