PCPD: Plant cytochrome P450 database and web-based tools for structural construction and ligand docking

Wang, Hui; Wang, Qian; Liu, Yuqian; Liao, Xiaoping; Chu, Huanyu; Chang, Hong; Cao, Yang; Li, Zhigang; Zhang, Tongcun; Cheng, Jian; Jiang, Huifeng

doi:10.1016/j.synbio.2021.04.004

Cited by 35 publications

(22 citation statements)

References 76 publications

(70 reference statements)

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“…In plants, members of CYP71 clan have been categorized into A-type, and rest into non-A type (Paquette et al 2000, Nelson 1999). In spite of quite a number of sequence identified, very less members has been biochemically characterized (Wang et al 2021). The members of CYP71 clan are involved in terpenoids, amino acid derivatives, hormone precursors, and alkaloids metabolism (Nelson and Werck-Reichhart 2011).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide investigation of Cytochrome P450 superfamily of Aquilaria agallocha: association with terpenoids and phenylpropanoids biosynthesis

Das

Begum

Akhtar

et al. 2022

Preprint

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P450 superfamily (CYPs) has been known as contributors to the metabolites's diversity and their promiscuous nature has led to the flexibility in substrate specificity and functional diversity. Current study was designed to investigate CYPs in the genome of an agarwood producing plant species named Aquilaria agallocha. Agarwood, the resinous fragrant wood with numerous phytochemicals, produced when an Aquilaria plant respond to wound and microbial infection. These chemicals are of great interest to industries ascribing it a high economic value. However, the pathways for the biosynthesis of these metabolites have not been studied in context of Aquilaria CYPs. We identified 136 A. agallocha CYP proteins from the genome, characterized and classified them into 8 clans and 38 families. Functional analysis unveiled their participation in terpenoids, phenolics, flavonoids and other valuable metabolites biosynthesis. Conserved motifs were detected and evolutionary analysis revealed duplicated and orthologous pairs. Potential members for the biosynthesis of sesquiterpenoids and phenylpropanoids reported in Aquilaria and agarwood were elucidated and validated through expression profiles in stress induced callus tissues and infected Aquilaria tress. This study provides a strong foundation for biochemical characterization of Aquilaria CYPs which will aid heterologous production of valuable phytochemicals and untangle molecular mechanism of agarwood formation.

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Section: Introductionmentioning

confidence: 99%

Genome-wide investigation of Cytochrome P450 superfamily of Aquilaria agallocha: association with terpenoids and phenylpropanoids biosynthesis

Das

Begum

Akhtar

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Wang and colleagues establish a plant P450 database (PCPD: http://p450.biodesign.ac.cn/ ), in which the sequences, structures and functions of the 181 plant P450s are included, and a web service based on a high-resolution P450 structure prediction process (PCPCM) and a ligand docking process (PCPLD). This work also introduces a universal strategy for the mining and functional analysis of P450 enzymes [ 19 ]. Synthetic biology is currently a raising and promising tool for biointelligent manufacturing.…”

Section: Biotechnological Methods and Toolsmentioning

confidence: 99%

Editorial for “Biointelligent manufacturing in Memorium of Arnold (Arny) L. Demain”

Gao

Nielsen

2022

Synthetic and Systems Biotechnology

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“…The peripheral localisation of CYP98A196 does not co-localize with the plasma membrane signal, which surrounds the cell in a uniform manner (Figure 6E). The signal of CYP98A196-EYFP surrounds the autofluorescence of chlorophyll, as depicted in Figure 6G To examine the structural differences of CYP98A members producing 3-hydroxyphloretin in vivo to those of M. × domestica, we constructed protein models using PCPD server, which combines structural homology and molecular dynamics simulation optimised for plant cytochrome P450s to predict the final protein model (Wang et al, 2021). Then, we carried out a protein-ligand docking by PCPLD using phloretin as potential ligand to predict the position and orientation of phloretin in CYP98A196 protein model.…”

Section: Characterisation Of Dhc3h Protein By Subcellular Localizatio...mentioning

confidence: 99%

“…Remarkably, these differences are sufficient to produce proteins lacking 3-hydroxylase activity towards phloretin in yeast. Aiming to explore the structural basis that could underlie differences in activity, we conducted a protein model prediction by PCPD, a plant cytochrome P450 database that combines AlphaFold2, molecular dynamics (MD) simulation and ligand docking to score and determine the final model (Wang et al, 2021). AlphaFold has greatly improved the accuracy of protein structure prediction, outperforming standard algorithms (Jumper et al, 2021).…”

Section: Functional Characterisation Of 3hydroxylase Involved In the ...mentioning

confidence: 99%

“…AlphaFold has greatly improved the accuracy of protein structure prediction, outperforming standard algorithms (Jumper et al, 2021). Integration of MDsimulation and ligand docking process optimised for cytochrome P450s (PCPLD) resulted in the construction of a broad database specifically designed for simulation of plant cytochrome P450s (Wang et al, 2021). Using PCPD and PCPLD, we found significant differences in DHC3H compared to M. × domestica.…”

Section: Functional Characterisation Of 3hydroxylase Involved In the ...mentioning

confidence: 99%

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De novo transcriptome assembly and functional analysis reveal a dihydrochalcone 3-hydroxylase(DHC3H) of wild Malus species that produces sieboldin in vivo

et al. 2022

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Sieboldin is a specialised secondary metabolite of the group of dihydrochalcones (DHC), found in high concentrations only in some wild Malus species, closely related to the domesticated apple (Malus × domestica L.). To date, the first committed step towards the biosynthesis of sieboldin remains unknown. In this study, we combined transcriptomic analysis and a de novo transcriptome assembly to identify two putative 3-hydroxylases in two wild Malus species (Malus toringo (K. Koch) Carriere syn. sieboldii Rehder, Malus micromalus Makino) whose DHC profile is dominated by sieboldin. We assessed the in vivo activity of putative candidates to produce 3-hydroxyphloretin and sieboldin by de novo production in Saccharomyces cerevisiae. We found that CYP98A proteins of wild Malus accessions (CYP98A195, M. toringo and CYP98A196, M. micromalus) were able to produce 3-hydroxyphloretin, ultimately leading to sieboldin accumulation by co-expression with PGT2. CYP98A197-198 genes of M. × domestica, however, were unable to hydroxylate phloretin in vivo. CYP98A195-196 proteins exerting 3-hydroxylase activity co-localised with an endoplasmic reticulum marker. CYP98A protein model from wild accessions showed mutations in key residues close to the ligand pocket predicted using phloretin for protein docking modelling. These mutations are located within known substrate recognition sites of cytochrome P450s, which could explain the acceptance of phloretin in CYP98A protein of wild accessions. Screening a Malus germplasm collection by HRM marker analysis for CYP98A genes identified three clusters that correspond to the alleles of domesticated and wild species. Moreover, CYP98A isoforms identified in M. toringo and M. micromalus correlate with the accumulation of sieboldin in other wild and hybrid Malus genotypes. Taken together, we provide the first evidence of an enzyme producing sieboldin in vivo that could be involved in the key hydroxylation step towards the synthesis of sieboldin in Malus species.

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PCPD: Plant cytochrome P450 database and web-based tools for structural construction and ligand docking

Cited by 35 publications

References 76 publications

Genome-wide investigation of Cytochrome P450 superfamily of Aquilaria agallocha: association with terpenoids and phenylpropanoids biosynthesis

Genome-wide investigation of Cytochrome P450 superfamily of Aquilaria agallocha: association with terpenoids and phenylpropanoids biosynthesis

Editorial for “Biointelligent manufacturing in Memorium of Arnold (Arny) L. Demain”

De novo transcriptome assembly and functional analysis reveal a dihydrochalcone 3-hydroxylase(DHC3H) of wild Malus species that produces sieboldin in vivo

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