Halogenases for biosynthetic pathway engineering: Toward new routes to naturals and non-naturals

Abstract

Nature's repertoire of bio-halogenase enzymes is intriguing with halogenases from various natural product biosynthetic clusters that carry out site and region-specific halogenation of diverse bioactive precursors and molecules. Currently, we have a comprehensive catalogue of cryptic and non-cryptic halogenases that act on simple to complex aliphatic and aromatic molecular scaffolds. This will open up further synthetic and biosynthetic opportunities for C-H activation, ring formation and functionalization of different molecular structures. In fact, halogenases were exploited over the years for these potential applications, to replace traditional chemical halogenation chemistries toward creating economical and environmentally benign methodologies and also for biosynthetic pathways. This review will discuss our advances in utilizing biohalogenases to generate both in vivo and in vitro biosynthetic pathways; summarizing all naturals and non-naturals that are synthesized with a direct bio-halogenase incorporation.

Versatile and Facile One-Pot Biosynthesis for Amides and Carboxylic Acids in E. coli by Engineering Auxin Pathways of Plant Microbiomes

“…Flavin-dependent halogenase (Fl-Hal)-based selective activation of aromatic C–H positions has transformed integrated chemo–bio-synthesis in recent years. − Fl-Hal enzymes PrnA, SttH, and PyrH for regiospecifically halogenated tryptophan 7, 6, and 5 positions, respectively, were studied extensively by different groups, providing an effective catalyst control for the followed Pd-based cross-coupling chemistries. − As we identified that iaaM and iaaH enzymes could accept halogenated compounds at different positions, the possibility of utilizing Fl-Hals (PrnA, PyrH, and SttH) to install halogen bonds in tryptophan was explored. The halogenated tryptophan could be further processed via IAM pathway enzymes generating site-specific halogenated IAMs and IAAs.…”

ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways

“…However, haloperoxidases, another group of peroxidases, mediate reactions of halide ions with hydrogen peroxide [ 100 ]. This class has identified three enzymes in mammals: lactoperoxidase, myeloperoxidase (MPO), and eosinophil peroxidase.…”

Halogenation in Fungi: What Do We Know and What Remains to Be Discovered?

“…Nowadays, computational methods are the easiest way to detect potential halogenating proteins for example using genome-mining tools like antiSMASH or Blastp [ 24 , 44 ]. These genome-mining methods are very useful for the detection of enzymes present in biosynthetic gene clusters (mainly for FDHs) [ 45 , 46 , 47 ].…”