Characterization and reconstitution of a new fungal type III polyketide synthase from Aspergillus oryzae

Yu, Dayu; Zeng, Jia; Dong, Chen; Zhan, Jixun

doi:10.1016/j.enzmictec.2010.02.011

Cited by 25 publications

(13 citation statements)

References 21 publications

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“…The second group consists of CsyA (S‐3‐L, S‐4‐A) and CsyB (S‐4a‐L) . CsyA that is heterologously expressed in Escherichia coli can use acyl‐CoAs of various chain lengths (C 4 –C 18 and C 10 –C 18 ) with two and three malonyl‐CoA units to produce triketide and tetraketide pyrones (L‐3‐L and L‐4‐L), respectively . CsyB condenses a short‐chain (C 2 –C 10 ) fatty acyl‐CoA starter with a malonyl‐CoA to produce a β‐keto fatty acyl‐CoA (S‐2‐X), which is condensed with an acetoacetyl‐CoA to produce a 3‐acetyl‐6‐alkyl‐4‐hydroxypyran‐2‐one (AcAP) (S‐4a‐L); AcAP can be further oxidized …”

Section: Experimentally Characterized Type III Pksmentioning

confidence: 99%

Type III Polyketide Synthases: Functional Classification and Phylogenomics

2016

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Polyketide synthases (PKSs) catalyze the sequential condensation of simple acetate units to produce a large class of natural products, including pharmacologically valuable compounds. PKSs are classified into three types on the basis of their domain structures; type III PKSs have the simplest domain structure, although their products have various structures and functions. The sequence–function relationship is fundamental for predicting enzyme functions, but it has not been well investigated in type III PKSs to date. Consequently, the current methods for predicting type III PKS functions are still immature in comparison with those that target type I/II PKSs. In this review we summarize the current functional and phylogenomic knowledge about type III PKSs and propose a new classification of their enzymatic reactions. We also discuss possible directions for the development of better computational tools for functional prediction of type III PKS homologues.

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Section: Experimentally Characterized Type III Pksmentioning

confidence: 99%

Type III Polyketide Synthases: Functional Classification and Phylogenomics

2016

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“…7). CsyA was also reconstituted in Escherichia coli for the production of polyketides without exogenously supplied starter units, indicating that it can be used as a biocatalytic tool for the synthesis of pyrone compounds both in vivo and in vitro (43). Interestingly, an independent study by Seshime and coworkers showed that expression of CsyA in A. oryzae M-2-3 has led to the production of 3,5-dihydroxybenzoic acid.…”

Section: Fungal Type III Pkssmentioning

confidence: 99%

Type III polyketide synthases in natural product biosynthesis

et al. 2012

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SummaryPolyketides represent an important class of biologically active and structurally diverse compounds in nature. They are synthesized from acyl-coenzyme A substrates by polyketide synthases (PKSs). PKSs are classified into three groups: types I, II, and III. This article introduces recent studies on type III PKSs identified from plants, bacteria, and fungi, and describes the catalytic functions of these enzymes in detail. Plant type III PKSs have been widely studied, as exemplified by chalcone synthase, which plays an important role in the synthesis of plant metabolites. Bacterial type III PKSs fall into five groups, many of which were identified from Streptomyces, a genus that has been well known for its production of bioactive molecules and genetic alterability. Although it was believed that type III PKSs exist exclusively in plants and bacteria, recent fungal genome sequencing projects and biochemical studies revealed the presence of type III PKSs in filamentous fungi, which provides a new chance to study fungal secondary metabolism and synthesize ''unnatural'' natural products. Type III PKSs have been used for the biosynthesis of novel molecules through precursordirected and structure-based mutagenesis approaches.2012 IUBMB IUBMB Life, 64(4): [285][286][287][288][289][290][291][292][293][294][295] 2012

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“…Slf14 produces six alkylresorcinols from long starter units when heterologously expressed in Saccharomyces cerevisiae (Yan et al, 2018). Similarly, CsyA produces in A. oryzae three related compounds, with the major product being the pentaketide 3,5-dihydroxybenzoic acid (Seshime et al, 2010b), while recombinant CsyA yields tri and tetraketide pyrones from C4 to C18 starter units, with a preference for C6 and C7 fatty acyl-CoAs (Yu et al, 2010). In A. oryzae, CsyB produces csypyrones from acetoacetyl-CoA starter unit and a ketoacyl diketide unit (Seshime et al, 2010a;Hashimoto et al, 2013;Mori et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Evolutionary Histories of Type III Polyketide Synthases in Fungi

Navarro-Muñoz

Collemare

2020

Front. Microbiol.

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Type III polyketide synthases (PKSs) produce secondary metabolites with diverse biological activities, including antimicrobials. While they have been extensively studied in plants and bacteria, only a handful of type III PKSs from fungi has been characterized in the last 15 years. The exploitation of fungal type III PKSs to produce novel bioactive compounds requires understanding the diversity of these enzymes, as well as of their biosynthetic pathways. Here, phylogenetic and reconciliation analyses of 522 type III PKSs from 1,193 fungal genomes revealed complex evolutionary histories with massive gene duplications and losses, explaining their discontinuous distribution in the fungal tree of life. In addition, horizontal gene transfer events from bacteria to fungi and, to a lower extent, between fungi, could be inferred. Ancestral gene duplication events have resulted in the divergence of eight phylogenetic clades. Especially, two clades show ancestral linkage and functional co-evolution between a type III PKS and a reducing PKS genes. Investigation of the occurrence of protein domains in fungal type III PKS predicted gene clusters highlighted the diversity of biosynthetic pathways, likely reflecting a large chemical landscape. Type III PKS genes are most often located next to genes encoding cytochrome P450s, MFS transporters and transcription factors, defining ancestral core gene clusters. This analysis also allowed predicting gene clusters for the characterized fungal type III PKSs and provides working hypotheses for the elucidation of the full biosynthetic pathways. Altogether, our analyses provide the fundamental knowledge to motivate further characterization and exploitation of fungal type III PKS biosynthetic pathways.

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Characterization and reconstitution of a new fungal type III polyketide synthase from Aspergillus oryzae

Cited by 25 publications

References 21 publications

Type III Polyketide Synthases: Functional Classification and Phylogenomics

Type III Polyketide Synthases: Functional Classification and Phylogenomics

Type III polyketide synthases in natural product biosynthesis

Evolutionary Histories of Type III Polyketide Synthases in Fungi

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