The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium

Shishido, Tânia Keiko; Jokela, Jouni; Humisto, Anu; Suurnäkki, Suvi; Wahlsten, Matti; Alvarenga, Danillo Oliveira; Sivonen, Kaarina; Fewer, David P.

doi:10.3390/md17050271

Cited by 23 publications

(18 citation statements)

References 65 publications

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“…Therefore, strains that do not produce MCs can result from inactivation either by point mutation, or by partial or complete deletion of mcy genes [36,57,59,60]. Recently, Shishido et al [61] reported that the mcy gene cluster did not encode all enzymes for the synthesis of rare variants of MC that contain a selection of homo-amino acids by the benthic cyanobacterium Phormidium sp. LP904c, but may instead activate homo-amino acids produced during the synthesis of anabaenopeptins.…”

Section: Biosynthesis Of Microcystinsmentioning

confidence: 99%

Structural Diversity, Characterization and Toxicology of Microcystins

Bouaı̈cha

Miles

Beach

et al. 2019

Toxins

298

192

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Hepatotoxic microcystins (MCs) are the most widespread class of cyanotoxins and the one that has most often been implicated in cyanobacterial toxicosis. One of the main challenges in studying and monitoring MCs is the great structural diversity within the class. The full chemical structure of the first MC was elucidated in the early 1980s and since then, the number of reported structural analogues has grown steadily and continues to do so, thanks largely to advances in analytical methodology. The structures of some of these analogues have been definitively elucidated after chemical isolation using a combination of techniques including nuclear magnetic resonance, amino acid analysis, and tandem mass spectrometry (MS/MS). Others have only been tentatively identified using liquid chromatography-MS/MS without chemical isolation. An understanding of the structural diversity of MCs, the genetic and environmental controls for this diversity and the impact of structure on toxicity are all essential to the ongoing study of MCs across several scientific disciplines. However, because of the diversity of MCs and the range of approaches that have been taken for characterizing them, comprehensive information on the state of knowledge in each of these areas can be challenging to gather. We have conducted an in-depth review of the literature surrounding the identification and toxicity of known MCs and present here a concise review of these topics. At present, at least 279 MCs have been reported and are tabulated here. Among these, about 20% (55 of 279) appear to be the result of chemical or biochemical transformations of MCs that can occur in the environment or during sample handling and extraction of cyanobacteria, including oxidation products, methyl esters, or post-biosynthetic metabolites. The toxicity of many MCs has also been studied using a range of different approaches and a great deal of variability can be observed between reported toxicities, even for the same congener. This review will help clarify the current state of knowledge on the structural diversity of MCs as a class and the impacts of structure on toxicity, as well as to identify gaps in knowledge that should be addressed in future research.

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Section: Biosynthesis Of Microcystinsmentioning

confidence: 99%

Structural Diversity, Characterization and Toxicology of Microcystins

Bouaı̈cha

Miles

Beach

et al. 2019

Toxins

298

192

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“…While production of Mdha 7 were reported for Planktothrix agardhii NIVA CYA 126/8 [12], Microcystis aeruginosa NIES 843 and Fischerella sp. CENA161 [3,6], Dha 7 was the only AA residue reported for M. aeruginosa K-139 [12]. Among the investigated species in this study, Mdhb 7 formation was only reported for Nostoc sp.…”

Section: Resultsmentioning

confidence: 87%

“…Among the investigated species in this study, Mdhb 7 formation was only reported for Nostoc sp. 152 [27] that also produced Dha 7 , MeSer 7 and Mdha 7 [12,25] containing MCs (Table 2).…”

Section: Resultsmentioning

confidence: 99%

Examination of Substrate Specificity of the First Adenylation Domain in mcyA Module Involved in Microcystin Biosynthesis

Yaman

Yılmaz

2020

International Journal of Secondary Metabolite

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The cyanotoxin microcystin (MC) is a secondary metabolite, synthesized by nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymes. It has many isoforms and the mechanism of its diversity is not well understood. One of the MC synthetase genes, mcyA, codes for the McyA module containing two adenylation (A) domains. The first domain, McyA-A1, generally binds to L-serine (L-ser). Then the N-methyl transferase (NMT) domain converts L-Ser into N-methyldehydroalanine (Mdha), which usually occupies position 7 on the MC molecule. However, various other amino acids (AAs) might also be present at this position. In this study, bioinformatic analyses of selected cyanobacteria were performed to understand whether genetic information in the first adenylation domain of mcyA could explain incorporation of different AAs at position 7 of the MC molecule. Binding pocket signatures of McyA-A1 and putative activated AAs were determined via various bioinformatics tools. Maximum likelihood phylogenetic trees of full length mcyA, mcyA-A1 and 16S rRNA genes were prepared in Mega 6. Phylogenetic analysis of mcyA-A1 nucleotide sequences was in agreement with the predictions of activated AAs by McyA-A1. In comparison with the 16S rRNA and full length mcyA gene trees, mcyA-A1 phylogenetic trees suggested horizontal transfer of the A domain in either Planktothrix agardhii (Gomont) Anagnostidis & Komárek or Planktothrix rubescens (De Candolle ex Gomont) Anagnostidis & Komárek strains. Predictions of activated AAs were generally in agreement with the chemically determined position 7 AAs. However, there were exceptions suggesting the multispecificity of the first A domain of McyA in some cyanobacteria.

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“…Presently, PKS and non-ribosomal peptide synthase (NRPS) are in the spotlight. In cyanobacteria, PKS has been known to synthesize toxic compounds such as microcystin ( Shishido et al, 2019 ) and swinholide ( Humisto et al, 2018 ). In some marine bacteria, PKS synthesize very long chain fatty acids, such as docosahexaenoic acids ( Okuyama et al, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

hetN and patS Mutations Enhance Accumulation of Fatty Alcohols in the hglT Mutants of Anabaena sp. PCC 7120

2020

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The heterocysts present in filamentous cyanobacteria such as Anabaena sp. PCC 7120 are known to be regulated by HetN and PatS, the repressors of heterocyst differentiation; therefore, the inactivation of these proteins will result in the formation of multiple heterocysts. To enhance the accumulation of fatty alcohols synthesized in the heterocyst, we introduced mutations of these repressors to increase heterocyst frequency. First, we isolated double mutants of hetN and patS and confirmed that the null mutation of these genes promoted higher frequencies of heterocyst formation and higher accumulation of heterocyst-specific glycolipids (Hgls) compared with its wild type. Next, we combined hetN and patS mutations with an hglT (encoding glycosyltransferase, an enzyme involved in Hgl synthesis) mutation to increase the accumulation of fatty alcohols since knockout mutation of hglT results in accumulation of very long chain fatty alcohol, the precursor of Hgl. We also observed retarded growth, lower chlorophyll content and up to a five-fold decrease in photosynthetic activity of the hetN / patS / hglT triple mutants. In contrast, the triple mutants showed three times higher heterocyst formation frequencies than the hglT single mutant and wild type. The production rate of fatty alcohol in the triple mutants attained a value 1.41 nmol/mL OD 730 , whereas accumulation of Hgls in the wild type was 0.90 nmol/mL OD 730 . Aeration of culture improved the accumulation of fatty alcohols in hetN / patS / hglT mutant cells up to 2.97 nmol/mL OD 730 compared with cells cultured by rotation. Our study outlines an alternative strategy for fatty alcohol production supported by photosynthesis and nitrogen fixation.

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The Biosynthesis of Rare Homo-Amino Acid Containing Variants of Microcystin by a Benthic Cyanobacterium

Cited by 23 publications

References 65 publications

Structural Diversity, Characterization and Toxicology of Microcystins

Structural Diversity, Characterization and Toxicology of Microcystins

Examination of Substrate Specificity of the First Adenylation Domain in mcyA Module Involved in Microcystin Biosynthesis

hetN and patS Mutations Enhance Accumulation of Fatty Alcohols in the hglT Mutants of Anabaena sp. PCC 7120

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