3,4-Dihydroxyphenylacetaldehyde synthase and cuticle formation in insects

Liao, Chenghong; Upadhyay, Archana; Liang, Jing; Han, Qian; Li, Jianyong

doi:10.1016/j.dci.2017.11.007

Cited by 21 publications

(19 citation statements)

References 88 publications

(99 reference statements)

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“…In Papaveraceae, on the other hand, we noticed a His-to-Leu substitution in the previously reported P. somniferum tyrosine decarboxylase 1 (PsTyDC1) (8) and a His-to-Tyr substitution in another Papaver bracteatum AAAD homolog. While the small-loop histidine is typically conserved among type II PLP decarboxylases and the broader type I aspartate aminotransferases, the same His-to-Asn substitution was previously observed in select insect AAAD proteins involved in 3,4-dihydroxyphenylacetaldehyde production necessary for insect soft cuticle formation (37,38). These sequence observations together with the proposed catalytic role of the small-loop histidine implicate that AAADs that carry substitutions at this highly conserved residue position may contain alternative enzymatic functions.…”

Section: Convergent Evolution Of Two Mechanistic Classes Of Aasssupporting

confidence: 55%

Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

Torrens-Spence

Chiang

Smith

et al. 2018

Preprint

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AbstractRadiation of the plant pyridoxal 5’-phosphate (PLP)-dependent aromatic L-amino acid decarboxylase (AAAD) family has yielded an array of paralogous enzymes exhibiting divergent substrate preferences and catalytic mechanisms. Plant AAADs catalyze either the decarboxylation or decarboxylation-dependent oxidative deamination of aromatic L-amino acids to produce aromatic monoamines or aromatic acetaldehydes, respectively. These compounds serve as key precursors for the biosynthesis of several important classes of plant natural products, including indole alkaloids, benzylisoquinoline alkaloids, hydroxycinnamic acid amides, phenylacetaldehyde-derived floral volatiles, and tyrosol derivatives. Here, we present the crystal structures of four functionally distinct plant AAAD paralogs. Through structural and functional analyses, we identify variable structural features of the substrate-binding pocket that underlie the divergent evolution of substrate selectivity toward indole, phenyl, or hydroxyphenyl amino acids in plant AAADs. Moreover, we describe two mechanistic classes of independently arising mutations in AAAD paralogs leading to the convergent evolution of the derived aldehyde synthase activity. Applying knowledge learned from this study, we successfully engineered a shortened benzylisoquinoline alkaloid pathway to produce (S)-norcoclaurine in yeast. This work highlights the pliability of the AAAD fold that allows change of substrate selectivity and access to alternative catalytic mechanisms with only a few mutations.SignificancePlants biosynthesize their own proteinogenic aromatic L-amino acids, namely L-phenylalanine, L-tyrosine and L-tryptophan, not only for building proteins but also for the production of a plethora of aromatic-amino-acid-derived natural products. Pyridoxal 5’-phosphate (PLP)-dependent aromatic L-amino acid decarboxylase (AAAD) family enzymes play important roles in channeling various aromatic L-amino acids into diverse downstream specialized metabolic pathways. Through comparative structural analysis of four functionally divergent plant AAAD proteins together with biochemical characterization and molecular dynamics simulations, we reveal the structural and mechanistic basis for the rich divergent and convergent evolutionary development within the plant AAAD family. Knowledge learned from this study aids our ability to engineer high-value aromatic-L-amino-acid-derived natural product biosynthesis in heterologous chassis organisms.

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Section: Convergent Evolution Of Two Mechanistic Classes Of Aasssupporting

confidence: 55%

Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

Torrens-Spence

Chiang

Smith

et al. 2018

Preprint

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“…The insect cuticle undergoes sclerotization, melanization and other physiological processes to play a protective role [8, 10, 11]. DOPAL synthase can catalyze the reaction from L-dopa to DOPAL, which can interact with free amino acids of CPs and directly participate in surface protein cross-linking [15–17]. However, there is no known biological effect of DOPAL in the postembryonic development of mosquitoes.…”

Section: Discussionmentioning

confidence: 99%

“…Structural and biochemical comparisons between DOPAL synthase and DDC in Drosophila identified that the key active site residue, Asn192, in insect DOPAL synthase can be used to distinguish all available insect DOPAL synthases from DDC sequences [15]. DOPAL has a high biological activity, which is directly linked to the CPs cross-linking through interaction of free amino acid groups on the CPs [11, 16, 17]. Early studies reported that DOPAL synthase-like protein, alpha methyldopa resistant (AMD-r), in Drosophila is resistant to the toxic compound, AMD.…”

Section: Introductionmentioning

confidence: 99%

RNA interference-mediated knockdown of 3, 4-dihydroxyphenylacetaldehyde synthase affects larval development and adult survival in the mosquito Aedes aegypti

Jing

Zhang

et al. 2019

Parasites Vectors

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Background The cuticle is an indispensable structure that protects the mosquito against adverse environmental conditions and prevents pathogen entry. While most cuticles are hard and rigid, some parts of cuticle are soft and flexible to allow movement and blood-feeding. It has been reported that 3, 4-dihydroxyphenylacetaldehyde (DOPAL) synthase is associated with flexible cuticle formation in Aedes aegypti . However, the molecular function of DOPAL synthase in the ontogenesis of mosquito remains largely unknown. In this study, we characterized gene expression profiles of DOPAL synthase and investigated its functions in larvae and female adults of Aedes agypti by RNAi. Results Our results suggest that the expression of DOPAL synthase is different during development and the transcriptional level reached its peak at the female white pupal stage, and DOPAL synthase was more highly expressed in the cuticle and midgut than other tissues in the adult. The development process from larva to pupa was slowed down strikingly by feeding the first-instar larvae with chitosan/ DOPAL synthase dsRNA nanoparticles. A qRT-PCR analysis confirmed that the dsRNA-mediated transcription of the DOPAL synthase was reduced > 50% in fourth-instar larvae. Meanwhile, larval molt was abnormal during development. Transmission electron microscopy results indicated that the formation of endocuticle and exocuticle was blocked. In addition, we detected that the ds DOPAL synthase RNA caused significant mortality when injected into the female adult mosquitoes. Conclusions Our findings demonstrate that DOPAL synthase plays a critical role in mosquito larval development and adult survival and suggest that DOPAL synthase could be a good candidate gene in RNAi intervention strategies in mosquito control. Electronic supplementary material The online version of this article (10.1186/s13071-019-3568-7) contains supplementary material, which is available to authorized users.

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“…The product of this enzyme, DHPAA, is hypothesized to be important in uncolored, flexible cuticle formation in insects, perhaps through aiding crosslinking of cuticular proteins (Fig. 6B) [55,56]. The Drosophila gene had been previously designated α‐methyldopa hypersensitive (amd) gene, based on observed sensitivity to AMD when the gene was mutated [57‐60].…”

Section: Amino Acid Aldehyde Synthasesmentioning

confidence: 99%

Emergence of oxygen‐ and pyridoxal phosphate‐dependent reactions

2020

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Pyridoxal 5′‐phosphate (PLP) is an organic cofactor employed by ~ 4% of enzymes. The structure of the PLP cofactor allows for the stabilization of carbanions through resonance. A small number of PLP‐dependent enzymes employ molecular oxygen as a cosubstrate. Here, we review the biological roles and possible mechanisms of these enzymes, and we observe that these enzymes are found in multiple protein families, suggesting that reaction with oxygen might have emerged de novo in several protein families and thus could be directed to emerge again through laboratory evolution experiments.

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3,4-Dihydroxyphenylacetaldehyde synthase and cuticle formation in insects

Cited by 21 publications

References 88 publications

Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

Structural basis for divergent and convergent evolution of catalytic machineries in plant aromatic amino acid decarboxylase proteins

RNA interference-mediated knockdown of 3, 4-dihydroxyphenylacetaldehyde synthase affects larval development and adult survival in the mosquito Aedes aegypti

Emergence of oxygen‐ and pyridoxal phosphate‐dependent reactions

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