Fujimori Danica Galonić, Walsh Christopher T
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Curr Opin Chem Biol. 2007 Oct;11(5):553-60. doi: 10.1016/j.cbpa.2007.08.002. Epub 2007 Sep 18.
The halogenation of thousands of natural products occurs during biosynthesis and often confers important functional properties. While haloperoxidases had been the default paradigm for enzymatic incorporation of halogens, via X+ equivalents into organic scaffolds, a combination of microbial genome sequencing, enzymatic studies and structural biology have provided deep new insights into enzymatic transfer of halide equivalents in three oxidation states. These are (1) the halide ions (X-) abundant in nature, (2) halogen atoms (X*), and (3) the X+ equivalents. The mechanism of halogen incorporation is tailored to the electronic demands of specific substrates and involves enzymes with distinct redox coenzyme requirements.
数千种天然产物的卤化反应发生在生物合成过程中,且常常赋予其重要的功能特性。虽然卤过氧化物酶一直是通过X⁺等价物将卤素酶促掺入有机支架的默认范例,但微生物基因组测序、酶学研究和结构生物学的结合为三种氧化态卤化物等价物的酶促转移提供了全新的深刻见解。这三种氧化态分别是:(1)自然界中丰富存在的卤离子(X⁻),(2)卤原子(X*),以及(3)X⁺等价物。卤素掺入的机制是根据特定底物的电子需求进行调整的,并且涉及具有不同氧化还原辅酶需求的酶。