Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

2011 ◽  
Vol 2 (11) ◽  
pp. 2182 ◽  
Author(s):  
Sabine Grüschow ◽  
Emma J. Rackham ◽  
Rebecca J. M. Goss
Keyword(s):  
Natural Product ◽  
Enzyme Promiscuity ◽  
Product Families

Evolutionary dynamics of natural product biosynthesis in bacteria

2020 ◽  
Vol 37 (4) ◽  
pp. 566-599 ◽  
Author(s):  
Marc G. Chevrette ◽  
Karina Gutiérrez-García ◽  
Nelly Selem-Mojica ◽  
César Aguilar-Martínez ◽  
Alan Yañez-Olvera ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Evolutionary Dynamics ◽  
Chemical Diversity ◽  
Enzyme Promiscuity ◽  
Evolutionary Mechanisms ◽  
Natural Product Biosynthesis ◽  
Metabolic Traits

We review known evolutionary mechanisms underlying the overwhelming chemical diversity of bacterial natural products biosynthesis, focusing on enzyme promiscuity and the evolution of enzymatic domains that enable metabolic traits.

scholarly journals Elucidating the Rimosamide-Detoxin Natural Product Families and Their Biosynthesis Using Metabolite/Gene Cluster Correlations

2016 ◽  
Vol 11 (12) ◽  
pp. 3452-3460 ◽  
Author(s):  
Ryan A. McClure ◽  
Anthony W. Goering ◽  
Kou-San Ju ◽  
Joshua A. Baccile ◽  
Frank C. Schroeder ◽  
...  
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Product Families

New Natural Product Families from an Environmental DNA (eDNA) Gene Cluster

2002 ◽  
Vol 124 (34) ◽  
pp. 9968-9969 ◽  
Author(s):  
Sean F. Brady ◽  
Carol J. Chao ◽  
Jon Clardy
Keyword(s):  
Natural Product ◽  
Gene Cluster ◽  
Environmental Dna ◽  
Product Families

scholarly journals Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lanthipeptides

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3001026
Author(s):  
Alexander M. Kloosterman ◽  
Peter Cimermancic ◽  
Somayah S. Elsayed ◽  
Chao Du ◽  
Michalis Hadjithomas ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Sequence Similarity ◽  
Genome Mining ◽  
Gene Clusters ◽  
Support Vector ◽  
Chemical Labeling ◽  
Product Families ◽  
Anticancer Properties ◽  
Modified Peptides

Microbial natural products constitute a wide variety of chemical compounds, many which can have antibiotic, antiviral, or anticancer properties that make them interesting for clinical purposes. Natural product classes include polyketides (PKs), nonribosomal peptides (NRPs), and ribosomally synthesized and post-translationally modified peptides (RiPPs). While variants of biosynthetic gene clusters (BGCs) for known classes of natural products are easy to identify in genome sequences, BGCs for new compound classes escape attention. In particular, evidence is accumulating that for RiPPs, subclasses known thus far may only represent the tip of an iceberg. Here, we present decRiPPter (Data-driven Exploratory Class-independent RiPP TrackER), a RiPP genome mining algorithm aimed at the discovery of novel RiPP classes. DecRiPPter combines a Support Vector Machine (SVM) that identifies candidate RiPP precursors with pan-genomic analyses to identify which of these are encoded within operon-like structures that are part of the accessory genome of a genus. Subsequently, it prioritizes such regions based on the presence of new enzymology and based on patterns of gene cluster and precursor peptide conservation across species. We then applied decRiPPter to mine 1,295 Streptomyces genomes, which led to the identification of 42 new candidate RiPP families that could not be found by existing programs. One of these was studied further and elucidated as a representative of a novel subfamily of lanthipeptides, which we designate class V. The 2D structure of the new RiPP, which we name pristinin A3 (1), was solved using nuclear magnetic resonance (NMR), tandem mass spectrometry (MS/MS) data, and chemical labeling. Two previously unidentified modifying enzymes are proposed to create the hallmark lanthionine bridges. Taken together, our work highlights how novel natural product families can be discovered by methods going beyond sequence similarity searches to integrate multiple pathway discovery criteria.

Synthetic studies toward inducamide C

2021 ◽  
Author(s):  
Ardalan A. Nabi ◽  
Lydia M. Scott ◽  
Daniel P. Furkert ◽  
Jonathan Sperry
Keyword(s):  
Natural Product ◽  
Structural Revision ◽  
Synthetic Studies

The rare benzoxazepine ring in the alkaloid inducamide C is unstable and prone to rearrangement, indicating that structural revision of the natural product may be necessary.

Lessons learned from the optimization of natural product based kinase inhibitors through molecular calculations

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
V Myrianthopoulos ◽  
P Magiatis ◽  
AL Skaltsounis ◽  
L Meijer ◽  
E Mikros
Keyword(s):  
Natural Product ◽  
Kinase Inhibitors ◽  
Lessons Learned ◽  
Molecular Calculations
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