How structural subtleties lead to molecular diversity for the type III polyketide synthases

Morita, Hiroyuki; Wong, Chin Piow; Abe, Ikuro

doi:10.1074/jbc.rev119.006129

Cited by 63 publications

(62 citation statements)

References 77 publications

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“…Given their strategic importance within the phenylpropanoid pathway we postulate that PKSs may have played a major role in the colonization of land, by providing the precursors for the synthesis of flavonoids (17) and sporopollenin (18,19). The type III PKS superfamily is a prime example of how the recruitment of an existing pathway led to the diversification of metabolic routes (12,20). PKS enzymes are likely derived from the -ketoacyl acyl carrier protein (ACP) synthases of fatty acid biosynthesis (21), as they share a protein fold (12,21).…”

Section: Introductionmentioning

confidence: 99%

“…More than 20 functionally different plant type III PKSs have been described ( Fig. 1) which share 30-95% sequence identity (20).…”

Section: Introductionmentioning

confidence: 99%

“…Among the most prominent members are chalcone synthases (CHSs) (20). CHSs catalyze the entry point of flavonoid metabolism and are well characterized in a number of model species (25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

“…CHSs catalyze the entry point of flavonoid metabolism and are well characterized in a number of model species (25)(26)(27). The diverse functions of the 20 types of enzymes arose due to their differences in (i) substrate specificities, (ii) numbers of condensations and (iii) cyclization reactions all of which are ultimately governed by the sequence of the genes which encode them (12,20).…”

Section: Introductionmentioning

confidence: 99%

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Kingdom-wide analysis of the evolution of the plant type III polyketide synthase superfamily

Naake

Maéda

Proost

et al. 2020

Preprint

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The emergence of type III polyketide synthases (PKSs) was a pre-requisite for the conquest of land by the green lineage. To study the deep evolutionary history of this key family, we used phylogenomic synteny network and phylogenetic analyses of whole-genome data from 126 species spanning the green lineage. This study thereby combined study of genomic location and context with changes in gene sequences. We found that two major clades, CHS and LAP5/6 homologs, evolved early by a segmental duplication event prior to the divergence of Bryophytes and Tracheophytes. We propose that the macroevolution of the type III PKS superfamily is governed by whole-genome duplications and triplications. Intriguingly, the combined phylogenetic and synteny analyses in this study shed new insights into changes in the genomic location and context that are retained for a longer time scale with more recent functional divergence captured by gene sequence alterations.PKSs are present in all land plants albeit in varying copy numbers. However, PKS were not found, or only found in low copy numbers, in the Chlorophyta, and are absent in Chlorokybophyceae, Mesostigmaphyceae and Coleochaetaphyceae of the Charophyta (see Supplementary Text). By contrast, type III PKS were detected in Penium margaritaceum (36). Synteny network analysis detects clade-specific and reaction type-specific clustersTo study the diversification of the type III PKS superfamily we followed a synteny network approach (32). Whole genomes of 126 species were compared in a pairwise manner, followed by robust block detection of regions containing type III PKS genes and network analysis to detect syntenic clusters within the network. The resultant network contained 706 vertices corresponding to syntenic regions containing single or multiple type III PKS genes of which 166 vertices corresponded to regions with tandem-duplicated genes from a total of 105 species ( Supplementary Table S2).Tandem-duplicated genes may play important roles in providing genetic redundancy, gene dosage balance, genetic robustness, and to provide an additional means for divergence in transcriptional regulation and protein sequence (37-40). The highest number of tandem-duplicated PKS genes in one syntenic region was 23 (Arachis duranensis, containing mainly 'R-4-A'-type PKS sequences, Fig. 1 and Fig. 2).Arachis ipaensis (21 genes) and Vitis vinifera (20 genes) had the second-and thirdhighest numbers of tandem-duplicated genes (also containing mostly 'R-4-A'-type sequences), respectively.

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Section: Introductionmentioning

confidence: 99%

“…More than 20 functionally different plant type III PKSs have been described ( Fig. 1) which share 30-95% sequence identity (20).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Kingdom-wide analysis of the evolution of the plant type III polyketide synthase superfamily

Naake

Maéda

Proost

et al. 2020

Preprint

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“…This short review focuses on the recently reported unusual "second generation" type III PKS enzymes [5], which mediate the fascinating chemistry of condensation reactions of CoA thioesters to generate various core structures of medicinally important plant secondary metabolites. For example, in the biogenesis of evocarpine in Rutaceae plants, two functionally distinct type III PKSs cooperatively mediate the condensation of three substrates (R 1 CO-CoA, R 2 CO-CoA, and malonyl-CoA) to generate the R 1 -C-R 2 core scaffold of the 2-alkylquinolone alkaloids [6].…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of medicinally important plant metabolites by unusual type III polyketide synthases

Abe

2020

J Nat Med

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Recent research progress on the "second generation" type III polyketide synthases is summarized. This class of enzymes catalyzes unusual condensation chemistries of CoA thioesters to generate various core structures of medicinally important plant secondary metabolites, including the R 1-C-R 2 scaffold of alkyl quinolones, curcuminoids, as well as the 8-azabicyclo[3.2.1] octane ring of tropane alkaloids. The discovery of this fascinating enzyme superfamily provides excellent opportunities for the manipulation of the enzyme reactions to expand the supply of natural and unnatural molecules for future drug development.

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Intrinsic Ability of the β‐Oxidation Pathway To Produce Bioactive Styrylpyrones

et al. 2022

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Naturally occurring α-pyrones with biological activities are mostly synthesised by polyketide synthases (PKSs) via iterative decarboxylative Claisen condensation steps. Remarkably, we found that some enzymes related to the fatty acid β-oxidation pathway in Escherichia coli, namely the CoA ligase FadD and the thiolases FadA and FadI, can synthesise styrylpyrones with phenylpropionic acids in vivo. The two thiolases directly utilise acetyl-CoA as an extender unit for carbon-chain elongation through a non-decarboxylative Claisen condensation, thus making the overall reaction more efficient in terms of carbon and energy consumption. Moreover, using a cell-free approach, different styrylpyrones were synthesised in vitro. Finally, targeted feeding experiments led to the detection of styrylpyrones in other species, demonstrating that the intrinsic ability of the β-oxidation pathway allows for the synthesis of such molecules in bacteria, revealing an important biological feature hitherto neglected.

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How structural subtleties lead to molecular diversity for the type III polyketide synthases

Cited by 63 publications

References 77 publications

Kingdom-wide analysis of the evolution of the plant type III polyketide synthase superfamily

Kingdom-wide analysis of the evolution of the plant type III polyketide synthase superfamily

Biosynthesis of medicinally important plant metabolites by unusual type III polyketide synthases

Intrinsic Ability of the β‐Oxidation Pathway To Produce Bioactive Styrylpyrones

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