scholarly journals Discovery and Biosynthesis of Guanipiperazine from a NRPS-like Pathway

2021 ◽  
Author(s):  
Jing Shi ◽  
Xiang Xu ◽  
Pei Yi Liu ◽  
Yi Ling Hu ◽  
Bo Zhang ◽  
...  
Keyword(s):  
Natural Products ◽  
Biologically Active ◽  
Nonribosomal Peptide ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases ◽  
Bacteria And Fungi ◽  
Active Natural

Nonribosomal peptide synthetases (NRPSs) are modular enzymes that use a thiotemplate mechanism to assemble the peptide backbones of structurally diverse and biologically active natural products in bacteria and fungi. Unlike...

scholarly journals Bacterial-like nonribosomal peptide synthetases produce cyclopeptides in the zygomycetous fungus Mortierella alpina

2020 ◽  
Author(s):  
Jacob M. Wurlitzer ◽  
Aleksa Stanišić ◽  
Ina Wasmuth ◽  
Sandra Jungmann ◽  
Dagmar Fischer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Mortierella Alpina ◽  
Bioactive Molecules ◽  
Fungal Genome ◽  
Nonribosomal Peptide ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases ◽  
Bacterial Origin ◽  
Basal Fungi

AbstractFungi are traditionally considered as reservoir of biologically active natural products. However, an active secondary metabolism has long not been attributed to early diverging fungi such as Mortierella spec. Here, we report on the biosynthesis of two series of cyclic pentapeptides, the malpicyclins and malpibaldins, as products of Mortierella alpina ATCC32222. The molecular structures of malpicyclins were elucidated by HR-MS/MS, Marfey’s method, and 1D and 2D NMR spectroscopy. In addition, malpibaldin biosynthesis was confirmed by HR-MS. Genome mining and comparative qRT-PCR expression analysis pointed at two pentamodular nonribosomal peptide synthetases (NRPS), malpicyclin synthetase MpcA and malpibaldin synthetase MpbA, as candidate biosynthetic enzymes. Heterologous production of the respective adenylation domains and substrate specificity assays proved promiscuous substrate selection and confirmed their respective biosynthetic roles. In stark contrast to known fungal NRPSs, MpbA and MpcA contain bacterial-like dual epimerase/condensation domains allowing the racemization of enzyme-tethered l-amino acids and the subsequent incorporation of d-amino acids into the metabolites. Phylogenetic analyses of both NRPS genes indicate a bacterial origin and a horizontal gene transfer into the fungal genome. This is the first report of nonribosomal peptide biosynthesis in basal fungi which highlights this paraphylum as novel and underrated resource of natural products.IMPORTANCEFungal natural compounds are industrially produced with application in antibiotic treatment, cancer medications and crop plant protection. Traditionally, higher fungi have been intensively investigated concerning their metabolic potential, but re-identification of already known compounds is frequently observed. Hence, alternative strategies to acquire novel bioactive molecules are required. We present the genus Mortierella as representative of the early diverging fungi as an underestimated resource of natural products. Mortierella alpina produces two families of cyclopeptides, denoted malpicyclins and malpibaldins, respectively, via two pentamodular nonribosomal peptide synthetases (NRPSs). These enzymes are much closer related to bacterial than to other fungal NRPSs, suggesting a bacterial origin of these NRPS genes in Mortierella. Both enzymes are the first biochemically characterized natural product biosynthesis enzymes of basal fungi. Hence, this report establishes early diverging fungi as prolific natural compound producers and sheds light on the origin of their biosynthetic capacity.

scholarly journals Bacterial-like nonribosomal peptide synthetases produce cyclopeptides in the zygomycetous fungus Mortierella alpina

2020 ◽  
Author(s):  
Jacob M. Wurlitzer ◽  
Aleksa Stanišić ◽  
Ina Wasmuth ◽  
Sandra Jungmann ◽  
Dagmar Fischer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Natural Products ◽  
Mortierella Alpina ◽  
Bioactive Molecules ◽  
Fungal Genome ◽  
Nonribosomal Peptide ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases ◽  
Bacterial Origin ◽  
Basal Fungi

Fungi are traditionally considered as reservoir of biologically active natural products. However, an active secondary metabolism has long not been attributed to early diverging fungi such as Mortierella spec. Here, we report on the biosynthesis of two series of cyclic pentapeptides, the malpicyclins and malpibaldins, as products of Mortierella alpina ATCC32222. The molecular structures of malpicyclins were elucidated by HR-MS/MS, Marfey's method, and 1D and 2D NMR spectroscopy. In addition, malpibaldin biosynthesis was confirmed by HR-MS. Genome mining and comparative qRT-PCR expression analysis pointed at two pentamodular nonribosomal peptide synthetases (NRPS), malpicyclin synthetase MpcA and malpibaldin synthetase MpbA, as candidate biosynthetic enzymes. Heterologous production of the respective adenylation domains and substrate specificity assays proved promiscuous substrate selection and confirmed their respective biosynthetic roles. In stark contrast to known fungal NRPSs, MpbA and MpcA contain bacterial-like dual epimerase/condensation domains allowing the racemization of enzyme-tethered l-amino acids and the subsequent incorporation of d-amino acids into the metabolites. Phylogenetic analyses of both NRPS genes indicate a bacterial origin and a horizontal gene transfer into the fungal genome. We report on the as yet unexplored nonribosomal peptide biosynthesis in basal fungi which highlights this paraphylum as novel and underrated resource of natural products. IMPORTANCE Fungal natural compounds are industrially produced with application in antibiotic treatment, cancer medications and crop plant protection. Traditionally, higher fungi have been intensively investigated concerning their metabolic potential, but re-identification of already known compounds is frequently observed. Hence, alternative strategies to acquire novel bioactive molecules are required. We present the genus Mortierella as representative of the early diverging fungi as an underestimated resource of natural products. Mortierella alpina produces two families of cyclopeptides, denoted malpicyclins and malpibaldins, respectively, via two pentamodular nonribosomal peptide synthetases (NRPSs). These enzymes are much closer related to bacterial than to other fungal NRPSs, suggesting a bacterial origin of these NRPS genes in Mortierella. Both enzymes were biochemically characterized and are involved in as yet unknown biosynthetic pathways of natural products in basal fungi. Hence, this report establishes early diverging fungi as prolific natural compound producers and sheds light on the origin of their biosynthetic capacity.

scholarly journals Nonribosomal Peptide Synthetases Involved in the Production of Medically Relevant Natural Products

2008 ◽  
Vol 5 (2) ◽  
pp. 191-211 ◽  
Author(s):  
Elizabeth A. Felnagle ◽  
Emily E. Jackson ◽  
Yolande A. Chan ◽  
Angela M. Podevels ◽  
Andrew D. Berti ◽  
...  
Keyword(s):  
Natural Products ◽  
Nonribosomal Peptide ◽  
Nonribosomal Peptide Synthetases ◽  
Peptide Synthetases

Biologically active natural products from Cassine viburnifolia

Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
T Grkovic ◽  
R Akee ◽  
J Evans ◽  
JM Collins ◽  
B O'Keefe
Keyword(s):  
Natural Products ◽  
Biologically Active ◽  
Active Natural

Synthetic studies on biologically active natural products by a chemicoenzymatic approach

Tetrahedron ◽  
1984 ◽  
Vol 40 (1) ◽  
pp. 145-152 ◽  
Author(s):  
Masaji Ohno ◽  
Yukishige Ito ◽  
Masafumi Arita ◽  
Tomoyuki Shibata ◽  
Kunitomo Adachi ◽  
...  
Keyword(s):  
Natural Products ◽  
Biologically Active ◽  
Synthetic Studies ◽  
Active Natural

Back to the Roots: Prediction of Biologically Active Natural Products from Ayurveda Traditional Medicine

2011 ◽  
Vol 30 (2-3) ◽  
pp. 181-187 ◽  
Author(s):  
Honey Polur ◽  
Tejal Joshi ◽  
Christopher T. Workman ◽  
Gandhidas Lavekar ◽  
Irene Kouskoumvekaki
Keyword(s):  
Natural Products ◽  
Traditional Medicine ◽  
Biologically Active ◽  
Active Natural

The Exploitation of Enzymatically-Derivedcis-1,2-Dihydrocatechols and Related Compounds in the Synthesis of Biologically Active Natural Products

2017 ◽  
Vol 18 (2) ◽  
pp. 239-264 ◽  
Author(s):  
Ehab S. Taher ◽  
Martin G. Banwell ◽  
Joshua N. Buckler ◽  
Qiao Yan ◽  
Ping Lan
Keyword(s):  
Natural Products ◽  
Biologically Active ◽  
Related Compounds ◽  
Active Natural
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