scholarly journals Genomes of novel Myxococcota reveal severely curtailed machineries for predation and cellular differentiation

2021 ◽  
Author(s):  
Chelsea L. Murphy ◽  
R. Yang ◽  
T. Decker ◽  
C. Cavalliere ◽  
V. Andreev ◽  
...  
Keyword(s):  
Social Behavior ◽  
Cellular Differentiation ◽  
Gene Clusters ◽  
Learning Approaches ◽  
Fruiting Body Formation ◽  
Biosynthetic Gene Clusters ◽  
Genes Encoding ◽  
Freshwater Spring ◽  
Aerobic Soil ◽  
Signal Transduction Systems

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, non-soil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring (Zodletone spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes, and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of thirteen distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g. FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine-learning approaches based on a set of 634 genes informative of social lifestyle predicted a non-social behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities, but encoded genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 Mya in response to the rise of soil as a distinct habitat on earth. Importance The Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcota are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota have been encountered in a wide range of non-soil, predominantly anaerobic habitats; and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes, and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of thirteen pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcota has occurred in response to soil formation as a distinct habitat on earth.

scholarly journals Genomes of novel Myxococcota reveal severely curtailed machineries for predation and cellular differentiation

2021 ◽  
Author(s):  
Chelsea Murphy ◽  
Cam Cavalliere ◽  
Jessica Cornell ◽  
Joel Higgs ◽  
Sergio Mares ◽  
...  
Keyword(s):  
Cellular Differentiation ◽  
Gene Clusters ◽  
Adaptation Strategy ◽  
Nitrite Reduction ◽  
Dissimilatory Sulfate Reduction ◽  
Learning Approaches ◽  
Niche Adaptation ◽  
Genes Encoding ◽  
Freshwater Spring ◽  
Aerobic Soil

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, non-soil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes, and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of thirteen distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g. FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine-learning approaches based on a set of 634 genes informative of social lifestyle predicted a non-social behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities, but encoded genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 Mya in response to the rise of soil as a distinct habitat on earth.

scholarly journals Bioinformatics and Experimental Analysis of Proteins of Two-Component Systems in Myxococcus xanthus

2007 ◽  
Vol 190 (2) ◽  
pp. 613-624 ◽  
Author(s):  
Xingqi Shi ◽  
Sigrun Wegener-Feldbrügge ◽  
Stuart Huntley ◽  
Nils Hamann ◽  
Reiner Hedderich ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Fruiting Body ◽  
Gene Clusters ◽  
Response Regulators ◽  
Fruiting Body Formation ◽  
Orphan Genes ◽  
Body Formation ◽  
Component Systems ◽  
Genes Encoding ◽  
Two Component Systems

ABSTRACT Proteins of two-component systems (TCS) have essential functions in the sensing of external and self-generated signals in bacteria and in the generation of appropriate output responses. Accordingly, in Myxococcus xanthus, TCS are important for normal motility and fruiting body formation and sporulation. Here we analyzed the M. xanthus genome for the presence and genetic organization of genes encoding TCS. Two hundred seventy-two TCS genes were identified, 251 of which are not part of che gene clusters. We report that the TCS genes are unusually organized, with 55% being orphan and 16% in complex gene clusters whereas only 29% display the standard paired gene organization. Hybrid histidine protein kinases and histidine protein kinases predicted to be localized to the cytoplasm are overrepresented among proteins encoded by orphan genes or in complex gene clusters. Similarly, response regulators without output domains are overrepresented among proteins encoded by orphan genes or in complex gene clusters. The most frequently occurring output domains in response regulators are involved in DNA binding and cyclic-di-GMP metabolism. Our analyses suggest that TCS encoded by orphan genes and complex gene clusters are functionally distinct from TCS encoded by paired genes and that the connectivity of the pathways made up of TCS encoded by orphan genes and complex gene clusters is different from that of pathways involving TCS encoded by paired genes. Experimentally, we observed that orphan TCS genes are overrepresented among genes that display altered transcription during fruiting body formation. The systematic analysis of the 25 orphan genes encoding histidine protein kinases that are transcriptionally up-regulated during development showed that 2 such genes are likely essential for viability and identified 7 histidine protein kinases, including 4 not previously characterized that have important function in fruiting body formation or spore germination.

scholarly journals Mining of Cyanobacterial Genomes Indicates That Plasmids Are Involved in the Production of Natural Products

2020 ◽  
Author(s):  
Rafael Popin ◽  
Danillo Alvarenga ◽  
Raquel Castelo-Branco ◽  
David Fewer ◽  
Kaarina Sivonen
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Biological Activities ◽  
Gene Clusters ◽  
Biosynthetic Pathways ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Chemical Structures ◽  
Wide Range ◽  
Genes Encoding

Abstract Background Microbial natural products have unique chemical structures and diverse biological activities. Cyanobacteria commonly possess a wide range of biosynthetic gene clusters to produce natural products. Several studies have mapped the distribution of natural product biosynthetic gene clusters in cyanobacterial genomes. However, little attention has been paid to natural product biosynthesis in plasmids. Some genes encoding cyanobacterial natural product biosynthetic pathways are believed to be dispersed by plasmids through horizontal gene transfer. Thus, we examined complete cyanobacterial genomes to assess if plasmids are involved in the production and dissemination of natural products by cyanobacteria.Results The 185 analyzed genomes possessed 1 to 42 gene clusters and an average of 10. In total, 1816 biosynthetic gene clusters were found. Approximately 95% of these clusters were present in chromosomes. The remaining 5% were present in plasmids, from which homologs of the biosynthetic pathways for aeruginosin, anabaenopeptin, ambiguine, cryptophycin, hassallidin, geosmin, and microcystin were manually curated. The cryptophycin pathway was previously described as active while the other gene cluster include all genes for biosynthesis. Approximately 12% of the 424 analyzed cyanobacterial plasmids contained homologs of genes involved in conjugation. Large plasmids, previously named as “chromids”, were also observed to be widespread in cyanobacteria. Sixteen cryptic natural product biosynthetic gene clusters and geosmin biosynthetic gene clusters were located in those mobile plasmids.Conclusion Homologues of genes involved in the production of toxins, protease inhibitors, odorous compounds, antimicrobials, antitumorals, and other unidentified natural products are located in cyanobacterial plasmids. Some of these plasmids are predicted to be conjugative. The present study provides in silico evidence that plasmids are involved in the distribution of natural product biosynthetic pathways in cyanobacteria.

scholarly journals Distribution and diversity of dimetal-carboxylate halogenases in cyanobacteria

2021 ◽  
Author(s):  
Nadia Eusebio ◽  
Adriana Rego ◽  
Nathaniel R. Glasser ◽  
Raquel Castelo-Branco ◽  
Emily P. Balskus ◽  
...  
Keyword(s):  
Genome Mining ◽  
Gene Clusters ◽  
Culture Collection ◽  
Acid Activation ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Genes Encoding ◽  
Fatty Acid Activation ◽  
Biological Catalysis

AbstractHalogenation is a recurring feature in natural products, especially those from marine organisms. The selectivity with which halogenating enzymes act on their substrates renders halogenases interesting targets for biocatalyst development. Recently, CylC – the first predicted dimetal-carboxylate halogenase to be characterized – was shown to regio- and stereoselectively install a chlorine atom onto an unactivated carbon center during cylindrocyclophane biosynthesis. Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. Due to its novelty in biological catalysis, selectivity and ability to perform C-H activation, this halogenase class is of considerable fundamental and applied interest. However, little is known regarding the diversity and distribution of these enzymes in bacteria. In this study, we used both genome mining and PCR-based screening to explore the genetic diversity and distribution of CylC homologs. While we found non-cyanobacterial homologs of these enzymes to be rare, we identified a large number of genes encoding CylC-like enzymes in publicly available cyanobacterial genomes and in our in-house culture collection of cyanobacteria. Genes encoding CylC homologs are widely distributed throughout the cyanobacterial tree of life, within biosynthetic gene clusters of distinct architectures. Their genomic contexts feature a variety of biosynthetic partners, including fatty-acid activation enzymes, type I or type III polyketide synthases, dialkylresorcinol-generating enzymes, monooxygenases or Rieske proteins. Our study also reveals that dimetal-carboxylate halogenases are among the most abundant types of halogenating enzymes in the phylum Cyanobacteria. This work will help to guide the search for new halogenating biocatalysts and natural product scaffolds.Data statementAll supporting data and methods have been provided within the article or through a Supplementary Material file, which includes 14 supplementary figures and 4 supplementary tables.

scholarly journals Identification of genes encoding squalestatin S1 biosynthesis and in vitro production of new squalestatin analogues

2016 ◽  
Vol 52 (41) ◽  
pp. 6777-6780 ◽  
Author(s):  
B. Bonsch ◽  
V. Belt ◽  
C. Bartel ◽  
N. Duensing ◽  
M. Koziol ◽  
...  
Keyword(s):  
Gene Clusters ◽  
Biosynthetic Gene ◽  
In Vitro Production ◽  
Biosynthetic Gene Clusters ◽  
Genes Encoding ◽  
Vitro Production

Biosynthetic gene clusters encoding the production of squalestatin S1 have been discovered and exploited to produce new analogs.

scholarly journals Presence, Mode of Action, and Application of Pathway Specific Transcription Factors in Aspergillus Biosynthetic Gene Clusters

2021 ◽  
Vol 22 (16) ◽  
pp. 8709
Author(s):  
Wenjie Wang ◽  
Yuchao Yu ◽  
Nancy P. Keller ◽  
Pinmei Wang
Keyword(s):  
Transcription Factor ◽  
Secondary Metabolites ◽  
Gene Clusters ◽  
Fungal Species ◽  
Relative Location ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Genes Encoding ◽  
Depth View ◽  
Fungal Secondary Metabolites

Fungal secondary metabolites are renowned toxins as well as valuable sources of antibiotics, cholesterol-lowering drugs, and immunosuppressants; hence, great efforts were levied to understand how these compounds are genetically regulated. The genes encoding for the enzymes required for synthesizing secondary metabolites are arranged in biosynthetic gene clusters (BGCs). Often, BGCs contain a pathway specific transcription factor (PSTF), a valuable tool in shutting down or turning up production of the BGC product. In this review, we present an in-depth view of PSTFs by examining over 40 characterized BGCs in the well-studied fungal species Aspergillus nidulans and Aspergillus fumigatus. Herein, we find BGC size is a predictor for presence of PSTFs, consider the number and the relative location of PSTF in regard to the cluster(s) regulated, discuss the function and the evolution of PSTFs, and present application strategies for pathway specific activation of cryptic BGCs.

scholarly journals Distribution and diversity of dimetal-carboxylate halogenases in cyanobacteria

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nadia Eusebio ◽  
Adriana Rego ◽  
Nathaniel R. Glasser ◽  
Raquel Castelo-Branco ◽  
Emily P. Balskus ◽  
...  
Keyword(s):  
Genome Mining ◽  
Gene Clusters ◽  
Culture Collection ◽  
Type I ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Rieske Proteins ◽  
Number Of Genes ◽  
Genes Encoding ◽  
Biological Catalysis

Abstract Background Halogenation is a recurring feature in natural products, especially those from marine organisms. The selectivity with which halogenating enzymes act on their substrates renders halogenases interesting targets for biocatalyst development. Recently, CylC – the first predicted dimetal-carboxylate halogenase to be characterized – was shown to regio- and stereoselectively install a chlorine atom onto an unactivated carbon center during cylindrocyclophane biosynthesis. Homologs of CylC are also found in other characterized cyanobacterial secondary metabolite biosynthetic gene clusters. Due to its novelty in biological catalysis, selectivity and ability to perform C-H activation, this halogenase class is of considerable fundamental and applied interest. The study of CylC-like enzymes will provide insights into substrate scope, mechanism and catalytic partners, and will also enable engineering these biocatalysts for similar or additional C-H activating functions. Still, little is known regarding the diversity and distribution of these enzymes. Results In this study, we used both genome mining and PCR-based screening to explore the genetic diversity of CylC homologs and their distribution in bacteria. While we found non-cyanobacterial homologs of these enzymes to be rare, we identified a large number of genes encoding CylC-like enzymes in publicly available cyanobacterial genomes and in our in-house culture collection of cyanobacteria. Genes encoding CylC homologs are widely distributed throughout the cyanobacterial tree of life, within biosynthetic gene clusters of distinct architectures (combination of unique gene groups). These enzymes are found in a variety of biosynthetic contexts, which include fatty-acid activating enzymes, type I or type III polyketide synthases, dialkylresorcinol-generating enzymes, monooxygenases or Rieske proteins. Our study also reveals that dimetal-carboxylate halogenases are among the most abundant types of halogenating enzymes in the phylum Cyanobacteria. Conclusions Our data show that dimetal-carboxylate halogenases are widely distributed throughout the Cyanobacteria phylum and that BGCs encoding CylC homologs are diverse and mostly uncharacterized. This work will help guide the search for new halogenating biocatalysts and natural product scaffolds.

scholarly journals Accumulation of S-Adenosyl-l-Methionine Enhances Production of Actinorhodin but Inhibits Sporulation in Streptomyces lividans TK23

2003 ◽  
Vol 185 (2) ◽  
pp. 592-600 ◽  
Author(s):  
Dong-Jin Kim ◽  
Jung-Hyun Huh ◽  
Young-Yell Yang ◽  
Choong-Min Kang ◽  
In-Hyung Lee ◽  
...  
Keyword(s):  
Cellular Differentiation ◽  
Antibiotic Production ◽  
Aerial Mycelium ◽  
Gene Clusters ◽  
Streptomyces Lividans ◽  
Northern Analysis ◽  
Transcription Activator ◽  
Biosynthetic Gene Clusters ◽  
S Gene

ABSTRACT S-Adenosyl-l-methionine synthetase (SAM-s) catalyzes the biosynthesis of SAM from ATP and l-methionine. Despite extensive research with many organisms, its role in Streptomyces sp. remains unclear. In the present study, the putative SAM-s gene was isolated from a spectinomycin producer, Streptomyces spectabilis. The purified protein from the transformed Escherichia coli with the isolated gene synthesized SAM from l-methionine and ATP in vitro, strongly indicating that the isolated gene indeed encoded the SAM-s protein. The overexpression of the SAM-s gene in Streptomyces lividans TK23 inhibited sporulation and aerial mycelium formation but enhanced the production of actinorhodin in both agar plates and liquid media. Surprisingly, the overexpressed SAM was proven by Northern analysis to increase the production of actinorhodin through the induction of actII-ORF4, a transcription activator of actinorhodin biosynthetic gene clusters. In addition, we found that a certain level of intracellular SAM is critical for the induction of antibiotic biosynthetic genes, since the control strain harboring only the plasmid DNA did not show any induction of actII-ORF4 until it reached a certain level of SAM in the cell. From these results, we concluded that the SAM plays important roles as an intracellular factor in both cellular differentiation and antibiotic production in Streptomyces sp.

Expanding the Natural Products Heterologous Expression Repertoire in the Model Cyanobacterium Anabaena sp. Strain PCC 7120: Production of Pendolmycin and Teleocidin B-4

2019 ◽  
Author(s):  
Patrick Videau ◽  
Kaitlyn Wells ◽  
Arun Singh ◽  
Jessie Eiting ◽  
Philip Proteau ◽  
...  
Keyword(s):  
Natural Products ◽  
Genome Mining ◽  
Gene Clusters ◽  
Combinatorial Biosynthesis ◽  
Test Case ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Cyanobacterium Anabaena ◽  
Anabaena Sp ◽  
Pcc 7120

Cyanobacteria are prolific producers of natural products and genome mining has shown that many orphan biosynthetic gene clusters can be found in sequenced cyanobacterial genomes. New tools and methodologies are required to investigate these biosynthetic gene clusters and here we present the use of <i>Anabaena </i>sp. strain PCC 7120 as a host for combinatorial biosynthesis of natural products using the indolactam natural products (lyngbyatoxin A, pendolmycin, and teleocidin B-4) as a test case. We were able to successfully produce all three compounds using codon optimized genes from Actinobacteria. We also introduce a new plasmid backbone based on the native <i>Anabaena</i>7120 plasmid pCC7120ζ and show that production of teleocidin B-4 can be accomplished using a two-plasmid system, which can be introduced by co-conjugation.

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