scholarly journals Multigenome analysis implicates miniature inverted-repeat transposable elements (MITEs) in metabolic diversification in eudicots

2018 ◽  
Vol 115 (28) ◽  
pp. E6650-E6658 ◽  
Author(s):  
Alexander M. Boutanaev ◽  
Anne E. Osbourn
Keyword(s):  
Transposable Elements ◽  
Inverted Repeat ◽  
Cluster Formation ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Terpene Synthase ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis ◽  
Plant Genomes

Plants produce a plethora of natural products, including many drugs. It has recently emerged that the genes encoding different natural product pathways may be organized as biosynthetic gene clusters in plant genomes, with >30 examples reported so far. Despite superficial similarities with microbes, these clusters have not arisen by horizontal gene transfer, but rather by gene duplication, neofunctionalization, and relocation via unknown mechanisms. Previously we reported that two Arabidopsis thaliana biosynthetic gene clusters are located in regions of the genome that are significantly enriched in transposable elements (TEs). Other plant biosynthetic gene clusters also harbor abundant TEs. TEs can mediate genomic rearrangement by providing homologous sequences that enable illegitimate recombination and gene relocation. Thus, TE-mediated recombination may contribute to plant biosynthetic gene cluster formation. TEs may also facilitate establishment of regulons. However, a systematic analysis of the TEs associated with plant biosynthetic gene clusters has not been carried out. Here we investigate the TEs associated with clustered terpene biosynthetic genes in multiple plant genomes and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Through investigation of the newly sequenced Amborella trichopoda, Aquilegia coerulea, and Kalanchoe fedtschenkoi genomes, we further show that the “block” mechanism of founding of biosynthetic gene clusters through duplication and diversification of pairs of terpene synthase and cytochrome P450 genes that is prevalent in the eudicots arose around 90–130 million years ago, after the appearance of the basal eudicots and before the emergence of the superrosid clade.

scholarly journals Identification of Putative Biosynthetic Gene Clusters for Tolyporphins in Multiple Filamentous Cyanobacteria

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 758
Author(s):  
Xiaohe Jin ◽  
Yunlong Zhang ◽  
Ran Zhang ◽  
Kathy-Uyen Nguyen ◽  
Jonathan S. Lindsey ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Filamentous Cyanobacterium ◽  
Biosynthetic Gene ◽  
Filamentous Cyanobacteria ◽  
Biosynthetic Gene Clusters ◽  
Common Component ◽  
Homology Searching ◽  
Similar Gene

Tolyporphins A–R are unusual tetrapyrrole macrocycles produced by the non-axenic filamentous cyanobacterium HT-58-2. A putative biosynthetic gene cluster for biosynthesis of tolyporphins (here termed BGC-1) was previously identified in the genome of HT-58-2. Here, homology searching of BGC-1 in HT-58-2 led to identification of similar BGCs in seven other filamentous cyanobacteria, including strains Nostoc sp. 106C, Nostoc sp. RF31YmG, Nostoc sp. FACHB-892, Brasilonema octagenarum UFV-OR1, Brasilonema octagenarum UFV-E1, Brasilonema sennae CENA114 and Oculatella sp. LEGE 06141, suggesting their potential for tolyporphins production. A similar gene cluster (BGC-2) also was identified unexpectedly in HT-58-2. Tolyporphins BGCs were not identified in unicellular cyanobacteria. Phylogenetic analysis based on 16S rRNA and a common component of the BGCs, TolD, points to a close evolutionary history between each strain and their respective tolyporphins BGC. Though identified with putative tolyporphins BGCs, examination of pigments extracted from three cyanobacteria has not revealed the presence of tolyporphins. Overall, the identification of BGCs and potential producers of tolyporphins presents a collection of candidate cyanobacteria for genetic and biochemical analysis pertaining to these unusual tetrapyrrole macrocycles.

Screening of tenuazonic acid production-inducing compounds and identification of NPD938 as a regulator of fungal secondary metabolism

2021 ◽  
Author(s):  
Takayuki Motoyama ◽  
Tomoaki Ishii ◽  
Takashi Kamakura ◽  
Hiroyuki Osada
Keyword(s):  
Secondary Metabolism ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Tenuazonic Acid ◽  
Cellular Functions ◽  
Biosynthetic Gene Clusters ◽  
Chemical Library ◽  
Tea Production ◽  
Fungal Secondary Metabolism

Abstract The control of secondary metabolism in fungi is essential for the regulation of various cellular functions. In this study, we searched the RIKEN Natural Products Depository (NPDepo) chemical library for inducers of tenuazonic acid (TeA) production in the rice blast fungus Pyricularia oryzae and identified NPD938. NPD938 transcriptionally induced TeA production. We explored the mode of action of NPD938 and observed that this compound enhanced TeA production via LAE1, a global regulator of fungal secondary metabolism. NPD938 could also induce production of terpendoles and pyridoxatins in Tolypocladium album RK99-F33. Terpendole production was induced transcriptionally. We identified the pyridoxatin biosynthetic gene cluster among transcriptionally induced secondary metabolite biosynthetic gene clusters. Therefore, NPD938 is useful for the control of fungal secondary metabolism.

scholarly journals Identification and distribution of gene clusters required for synthesis of sphingolipid metabolism inhibitors in diverse species of the filamentous fungus Fusarium

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Hye-Seon Kim ◽  
Jessica M. Lohmar ◽  
Mark Busman ◽  
Daren W. Brown ◽  
Todd A. Naumann ◽  
...  
Keyword(s):  
Polyketide Synthase ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Sphingolipid Metabolism ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Dehydrogenase Gene ◽  
Food And Feed ◽  
Feed Safety

Abstract Background Sphingolipids are structural components and signaling molecules in eukaryotic membranes, and many organisms produce compounds that inhibit sphingolipid metabolism. Some of the inhibitors are structurally similar to the sphingolipid biosynthetic intermediate sphinganine and are referred to as sphinganine-analog metabolites (SAMs). The mycotoxins fumonisins, which are frequent contaminants in maize, are one family of SAMs. Due to food and feed safety concerns, fumonisin biosynthesis has been investigated extensively, including characterization of the fumonisin biosynthetic gene cluster in the agriculturally important fungi Aspergillus and Fusarium. Production of several other SAMs has also been reported in fungi, but there is almost no information on their biosynthesis. There is also little information on how widely SAM production occurs in fungi or on the extent of structural variation of fungal SAMs. Results Using fumonisin biosynthesis as a model, we predicted that SAM biosynthetic gene clusters in fungi should include a polyketide synthase (PKS), an aminotransferase and a dehydrogenase gene. Surveys of genome sequences identified five putative clusters with this three-gene combination in 92 of 186 Fusarium species examined. Collectively, the putative SAM clusters were distributed widely but discontinuously among the species. We propose that the SAM5 cluster confers production of a previously reported Fusarium SAM, 2-amino-14,16-dimethyloctadecan-3-ol (AOD), based on the occurrence of AOD production only in species with the cluster and on deletion analysis of the SAM5 cluster PKS gene. We also identified SAM clusters in 24 species of other fungal genera, and propose that one of the clusters confers production of sphingofungin, a previously reported Aspergillus SAM. Conclusion Our results provide a genomics approach to identify novel SAM biosynthetic gene clusters in fungi, which should in turn contribute to identification of novel SAMs with applications in medicine and other fields. Information about novel SAMs could also provide insights into the role of SAMs in the ecology of fungi. Such insights have potential to contribute to strategies to reduce fumonisin contamination in crops and to control crop diseases caused by SAM-producing fungi.

scholarly journals Genomic analysis of siderophore β-hydroxylases reveals divergent stereocontrol and expands the condensation domain family

2019 ◽  
Vol 116 (40) ◽  
pp. 19805-19814 ◽  
Author(s):  
Zachary L. Reitz ◽  
Clifford D. Hardy ◽  
Jaewon Suk ◽  
Jean Bouvet ◽  
Alison Butler
Keyword(s):  
Predictive Power ◽  
Genome Mining ◽  
Genomic Analysis ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Peptide Synthetase ◽  
Condensation Domain

Genome mining of biosynthetic pathways streamlines discovery of secondary metabolites but can leave ambiguities in the predicted structures, which must be rectified experimentally. Through coupling the reactivity predicted by biosynthetic gene clusters with verified structures, the origin of the β-hydroxyaspartic acid diastereomers in siderophores is reported herein. Two functional subtypes of nonheme Fe(II)/α-ketoglutarate–dependent aspartyl β-hydroxylases are identified in siderophore biosynthetic gene clusters, which differ in genomic organization—existing either as fused domains (IβHAsp) at the carboxyl terminus of a nonribosomal peptide synthetase (NRPS) or as stand-alone enzymes (TβHAsp)—and each directs opposite stereoselectivity of Asp β-hydroxylation. The predictive power of this subtype delineation is confirmed by the stereochemical characterization of β-OHAsp residues in pyoverdine GB-1, delftibactin, histicorrugatin, and cupriachelin. The l-threo (2S, 3S) β-OHAsp residues of alterobactin arise from hydroxylation by the β-hydroxylase domain integrated into NRPS AltH, while l-erythro (2S, 3R) β-OHAsp in delftibactin arises from the stand-alone β-hydroxylase DelD. Cupriachelin contains both l-threo and l-erythro β-OHAsp, consistent with the presence of both types of β-hydroxylases in the biosynthetic gene cluster. A third subtype of nonheme Fe(II)/α-ketoglutarate–dependent enzymes (IβHHis) hydroxylates histidyl residues with l-threo stereospecificity. A previously undescribed, noncanonical member of the NRPS condensation domain superfamily is identified, named the interface domain, which is proposed to position the β-hydroxylase and the NRPS-bound amino acid prior to hydroxylation. Through mapping characterized β-OHAsp diastereomers to the phylogenetic tree of siderophore β-hydroxylases, methods to predict β-OHAsp stereochemistry in silico are realized.

scholarly journals A Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics

Cell ◽  
2014 ◽  
Vol 158 (6) ◽  
pp. 1402-1414 ◽  
Author(s):  
Mohamed S. Donia ◽  
Peter Cimermancic ◽  
Christopher J. Schulze ◽  
Laura C. Wieland Brown ◽  
John Martin ◽  
...  
Keyword(s):  
Human Microbiome ◽  
Gene Clusters ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Systematic Analysis

scholarly journals Biosynthetic Investigations of Lactonamycin and Lactonamycin Z: Cloning of the Biosynthetic Gene Clusters and Discovery of an Unusual Starter Unit

2007 ◽  
Vol 52 (2) ◽  
pp. 574-585 ◽  
Author(s):  
Xiujun Zhang ◽  
Lawrence B. Alemany ◽  
Hans-Peter Fiedler ◽  
Michael Goodfellow ◽  
Ronald J. Parry
Keyword(s):  
Gene Cluster ◽  
Genetic Locus ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Open Reading Frames ◽  
Antibacterial Drug ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Starter Unit ◽  
High Degree

ABSTRACT The antibiotics lactonamycin and lactonamycin Z provide attractive leads for antibacterial drug development. Both antibiotics contain a novel aglycone core called lactonamycinone. To gain insight into lactonamycinone biosynthesis, cloning and precursor incorporation experiments were undertaken. The lactonamycin gene cluster was initially cloned from Streptomyces rishiriensis. Sequencing of ca. 61 kb of S. rishiriensis DNA revealed the presence of 57 open reading frames. These included genes coding for the biosynthesis of l-rhodinose, the sugar found in lactonamycin, and genes similar to those in the tetracenomycin biosynthetic gene cluster. Since lactonamycin production by S. rishiriensis could not be sustained, additional proof for the identity of the S. rishiriensis cluster was obtained by cloning the lactonamycin Z gene cluster from Streptomyces sanglieri. Partial sequencing of the S. sanglieri cluster revealed 15 genes that exhibited a very high degree of similarity to genes within the lactonamycin cluster, as well as an identical organization. Double-crossover disruption of one gene in the S. sanglieri cluster abolished lactonamycin Z production, and production was restored by complementation. These results confirm the identity of the genetic locus cloned from S. sanglieri and indicate that the highly similar locus in S. rishiriensis encodes lactonamycin biosynthetic genes. Precursor incorporation experiments with S. sanglieri revealed that lactonamycinone is biosynthesized in an unusual manner whereby glycine or a glycine derivative serves as a starter unit that is extended by nine acetate units. Analysis of the gene clusters and of the precursor incorporation data suggested a hypothetical scheme for lactonamycinone biosynthesis.

scholarly journals Insights into the Evolution of Macrolactam Biosynthesis through Cloning and Comparative Analysis of the Biosynthetic Gene Cluster for a Novel Macrocyclic Lactam, ML-449

2009 ◽  
Vol 76 (1) ◽  
pp. 283-293 ◽  
Author(s):  
Hanne Jørgensen ◽  
Kristin F. Degnes ◽  
Alexander Dikiy ◽  
Espen Fjærvik ◽  
Geir Klinkenberg ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Evolutionary Relationship ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Side Chain ◽  
Small Ring ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
The Difference ◽  
High Level

ABSTRACT A new compound, designated ML-449, structurally similar to the known 20-membered macrolactam BE-14106, was isolated from a marine sediment-derived Streptomyces sp. Cloning and sequencing of the 83-kb ML-449 biosynthetic gene cluster revealed its high level of similarity to the BE-14106 gene cluster. Comparison of the respective biosynthetic pathways indicated that the difference in the compounds' structures stems from the incorporation of one extra acetate unit during the synthesis of the acyl side chain. A phylogenetic analysis of the β-ketosynthase (KS) domains from polyketide synthases involved in the biosynthesis of macrolactams pointed to a common ancestry for the two clusters. Furthermore, the analysis demonstrated the formation of a macrolactam-specific subclade for the majority of the KS domains from several macrolactam-biosynthetic gene clusters, indicating a closer relationship between macrolactam clusters than with the macrolactone clusters included in the analysis. Some KS domains from the ML-449, BE-14106, and salinilactam gene clusters did, however, show a closer relationship with KS domains from the polyene macrolide clusters, suggesting potential acquisition rather than duplication of certain PKS genes. Comparison of the ML-449, BE-14106, vicenistatin, and salinilactam biosynthetic gene clusters indicated an evolutionary relationship between them and provided new insights into the processes governing the evolution of small-ring macrolactam biosynthesis.

scholarly journals Formation and diversification of a paradigm biosynthetic gene cluster in plants

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhenhua Liu ◽  
Jitender Cheema ◽  
Marielle Vigouroux ◽  
Lionel Hill ◽  
James Reed ◽  
...  
Keyword(s):  
Complex Traits ◽  
Common Ancestor ◽  
Low Frequency ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Species Level ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Life And Death ◽  
Species Specific

Abstract Numerous examples of biosynthetic gene clusters (BGCs), including for compounds of agricultural and medicinal importance, have now been discovered in plant genomes. However, little is known about how these complex traits are assembled and diversified. Here, we examine a large number of variants within and between species for a paradigm BGC (the thalianol cluster), which has evolved recently in a common ancestor of the Arabidopsis genus. Comparisons at the species level reveal differences in BGC organization and involvement of auxiliary genes, resulting in production of species-specific triterpenes. Within species, the thalianol cluster is primarily fixed, showing a low frequency of deleterious haplotypes. We further identify chromosomal inversion as a molecular mechanism that may shuffle more distant genes into the cluster, so enabling cluster compaction. Antagonistic natural selection pressures are likely involved in shaping the occurrence and maintenance of this BGC. Our work sheds light on the birth, life and death of complex genetic and metabolic traits in plants.

scholarly journals Discovery of Gene Cluster for Mycosporine-Like Amino Acid Biosynthesis from Actinomycetales Microorganisms and Production of a Novel Mycosporine-Like Amino Acid by Heterologous Expression

2014 ◽  
Vol 80 (16) ◽  
pp. 5028-5036 ◽  
Author(s):  
Kiyoko T. Miyamoto ◽  
Mamoru Komatsu ◽  
Haruo Ikeda
Keyword(s):  
Amino Acid ◽  
Gene Cluster ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Dependent Manner ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Gram Positive ◽  
Content Type ◽  
Gram Positive Bacteria

ABSTRACTMycosporines and mycosporine-like amino acids (MAAs), including shinorine (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine), are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro- and macroalgae. These MAAs have the ability to protect these organisms from damage by environmental UV radiation. Although no reports have described the production of MAAs and the corresponding genes involved in MAA biosynthesis from Gram-positive bacteria to date, genome mining of the Gram-positive bacterial database revealed that two microorganisms belonging to the orderActinomycetales,Actinosynnema mirumDSM 43827 andPseudonocardiasp. strain P1, possess a gene cluster homologous to the biosynthetic gene clusters identified from cyanobacteria. When the two strains were grown in liquid culture,Pseudonocardiasp. accumulated a very small amount of MAA-like compound in a medium-dependent manner, whereasA. mirumdid not produce MAAs under any culture conditions, indicating that the biosynthetic gene cluster ofA. mirumwas in a cryptic state in this microorganism. In order to characterize these biosynthetic gene clusters, each biosynthetic gene cluster was heterologously expressed in an engineered host,Streptomyces avermitilisSUKA22. Since the resultant transformants carrying the entire biosynthetic gene cluster controlled by an alternative promoter produced mainly shinorine, this is the first confirmation of a biosynthetic gene cluster for MAA from Gram-positive bacteria. Furthermore,S. avermitilisSUKA22 transformants carrying the biosynthetic gene cluster for MAA ofA. mirumaccumulated not only shinorine and porphyra-334 but also a novel MAA. Structure elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which substitutesl-alanine for thel-serine of shinorine.

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