Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods

Abstract

The evolution of N-acetyltransfeases (NATs) seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT) has been extensively studied since it leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT), and also xenobiotic reactions (arylamine NAT or simply NAT). NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT) form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO) activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the circadian system. Therefore, the enzyme plays both unique and universal roles in insects. The unique role of iaaNATs in physiological regulation urges the targeting of this system for integrated pest management (IPM). We indeed showed a successful example of chemical compound screening with reconstituted enzyme and further attempts seem promising.

Critical Analysis of the Melanogenic Pathway in Insects and Higher Animals

“…In mammals, this protein catalyzes the essential first step in the formation of melatonin in the pineal gland and is associated with circadian rhythm. In insects, the aaNAT enzymes have different physiological roles [93,94]. They catalyze the formation of one of the two widely used insect cuticular sclerotizing precursors, NADA.…”

“…Acetyl CoA is the co-substrate for aaNAT in producing the N -acetyl derivatives of amines [95]. Recent studies point out that aaNAT suppresses melanin pigmentation in some insect cuticle [93,94,95,96,97,98,99]. The adult melanism ( mln ) mutant of silkworm Bombyx mori exhibits a strong black coloration in contrast to the wild type’s normal coloration [96].…”

Bm-iAANAT3: Expression and characterization of a novel arylalkylamine N-acyltransferase from Bombyx mori

“…Amine N -acetylation is catalyzed by the arylalkylamine N -acetyltransferases (AANATs, also known as arylalkylamine N -acyltransferases) [6,7] which are members of the GCN5-related N -acetyltransferase enzyme superfamily [8–10]. In insects, the iAANATs (iAANATs = insect AANATs) produce N -acetylserotonin, an intermediate in melatonin biosynthesis, and are thought to function in controlling melanism [11,12], the inactivation of biogenic amines [13,14], the sclerotization of the insect cuticle [14,15], and photoperiodism [7]. Our interest in the AANATs is derived from our work on the biosynthesis of the fatty acid amides [16,17], a family of cell signaling lipids [18].…”

“…We and others have found that AANAT-like (AANATL) enzymes will catalyze the formation of fatty acid amides from fatty acyl-CoA thioesters and the corresponding amines [17,19–21]. Database searches of insect genomes indicate that a number of iAANATs and iAANATLs could be expressed in a variety of insects [7,14,22]. Thus, insects should serve as model organisms to better understand the possible role played by the iAANATs and iAANATLs in the biosynthesis of N -acetyl- and N -acylarylalkylamides and to further define the biological function of these molecules.…”

Unraveling the Evolutionary Determinants of Sleep

“…Blue lines represent taxa in which multiple features of sleep have been confirmed but neither NREM nor REM sleep has been detected. Evolutionary relationships were replotted from [193, 209, 210]. …”