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Basidiomycete non-reducing polyketide synthases function independently of SAT domains
by
Gressler, Markus
, Hoffmeister, Dirk
, Wurlitzer, Jacob M.
, Rakhmanov, Malik
, Löhr, Nikolai A.
, Lackner, Gerald
in
Acetates
/ Acetic acid
/ Acyl carrier protein
/ Applied Microbiology
/ Biological products
/ Biomedical and Life Sciences
/ Biosynthesis
/ Biotechnology
/ Carboxylic acids
/ Enzyme engineering
/ Enzymes
/ Evolution
/ Genomes
/ Life Sciences
/ Literature reviews
/ Microbial Genetics and Genomics
/ Microbiology
/ Mushrooms
/ Mycology
/ Natural products
/ Orsellinic acid
/ Phylogenetics
/ Phylogeny
/ Physiological aspects
/ Plant Pathology
/ Polyketide synthase
/ Pseudogenes
/ SAT domain
2023
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Basidiomycete non-reducing polyketide synthases function independently of SAT domains
by
Gressler, Markus
, Hoffmeister, Dirk
, Wurlitzer, Jacob M.
, Rakhmanov, Malik
, Löhr, Nikolai A.
, Lackner, Gerald
in
Acetates
/ Acetic acid
/ Acyl carrier protein
/ Applied Microbiology
/ Biological products
/ Biomedical and Life Sciences
/ Biosynthesis
/ Biotechnology
/ Carboxylic acids
/ Enzyme engineering
/ Enzymes
/ Evolution
/ Genomes
/ Life Sciences
/ Literature reviews
/ Microbial Genetics and Genomics
/ Microbiology
/ Mushrooms
/ Mycology
/ Natural products
/ Orsellinic acid
/ Phylogenetics
/ Phylogeny
/ Physiological aspects
/ Plant Pathology
/ Polyketide synthase
/ Pseudogenes
/ SAT domain
2023
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Basidiomycete non-reducing polyketide synthases function independently of SAT domains
by
Gressler, Markus
, Hoffmeister, Dirk
, Wurlitzer, Jacob M.
, Rakhmanov, Malik
, Löhr, Nikolai A.
, Lackner, Gerald
in
Acetates
/ Acetic acid
/ Acyl carrier protein
/ Applied Microbiology
/ Biological products
/ Biomedical and Life Sciences
/ Biosynthesis
/ Biotechnology
/ Carboxylic acids
/ Enzyme engineering
/ Enzymes
/ Evolution
/ Genomes
/ Life Sciences
/ Literature reviews
/ Microbial Genetics and Genomics
/ Microbiology
/ Mushrooms
/ Mycology
/ Natural products
/ Orsellinic acid
/ Phylogenetics
/ Phylogeny
/ Physiological aspects
/ Plant Pathology
/ Polyketide synthase
/ Pseudogenes
/ SAT domain
2023
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Basidiomycete non-reducing polyketide synthases function independently of SAT domains
Journal Article
Basidiomycete non-reducing polyketide synthases function independently of SAT domains
2023
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Overview
Background
Non-reducing polyketide synthases (NR-PKSs) account for a major share of natural product diversity produced by both Asco- and Basidiomycota. The present evolutionary diversification into eleven clades further underscores the relevance of these multi-domain enzymes. Following current knowledge, NR-PKSs initiate polyketide assembly by an N-terminal starter unit:acyl transferase (SAT) domain that catalyzes the transfer of an acetyl starter from the acetyl-CoA thioester onto the acyl carrier protein (ACP).
Results
A comprehensive phylogenetic analysis of NR-PKSs established a twelfth clade from which three representatives, enzymes CrPKS1-3 of the webcap mushroom
Cortinarius rufoolivaceus
, were biochemically characterized. These basidiomycete synthases lack a SAT domain yet are fully functional hepta- and octaketide synthases in vivo. Three members of the other clade of basidiomycete NR-PKSs (clade VIII) were produced as SAT-domainless versions and analyzed in vivo and in vitro. They retained full activity, thus corroborating the notion that the SAT domain is dispensable for many basidiomycete NR-PKSs. For comparison, the ascomycete octaketide synthase atrochrysone carboxylic acid synthase (ACAS) was produced as a SAT-domainless enzyme as well, but turned out completely inactive. However, a literature survey revealed that some NR-PKSs of ascomycetes carry mutations within the catalytic motif of the SAT domain. In these cases, the role of the domain and the origin of the formal acetate unit remains open.
Conclusions
The role of SAT domains differs between asco- and basidiomycete NR-PKSs. For the latter, it is not part of the minimal set of NR-PKS domains and not required for function. This knowledge may help engineer compact NR-PKSs for more resource-efficient routes. From the genomic standpoint, seemingly incomplete or corrupted genes encoding SAT-domainless NR-PKSs should not automatically be dismissed as non-functional pseudogenes, but considered during genome analysis to decipher the potential arsenal of natural products of a given fungus.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
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