scholarly journals Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Li ◽  
Aymeric Leveau ◽  
Qiang Zhao ◽  
Qi Feng ◽  
Hengyun Lu ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Biosynthetic Gene Cluster ◽  
Gene Organization ◽  
Genome Plasticity ◽  
Biosynthetic Gene ◽  
Gene Deletions ◽  
Defense Compounds ◽  
Gene Pathway

AbstractNon-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat—the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a ‘self-poisoning’ scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.

Identification of the kinanthraquinone biosynthetic gene cluster by expression of an atypical response regulator

2021 ◽  
Vol 85 (3) ◽  
pp. 714-721
Author(s):  
Risa Takao ◽  
Katsuyuki Sakai ◽  
Hiroyuki Koshino ◽  
Hiroyuki Osada ◽  
Shunji Takahashi
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Secondary Metabolite ◽  
Response Regulator ◽  
Bac Library ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Gene Organization ◽  
Biosynthetic Gene ◽  
Streptomyces Sp

ABSTRACT Recent advances in genome sequencing have revealed a variety of secondary metabolite biosynthetic gene clusters in actinomycetes. Understanding the biosynthetic mechanism controlling secondary metabolite production is important for utilizing these gene clusters. In this study, we focused on the kinanthraquinone biosynthetic gene cluster, which has not been identified yet in Streptomyces sp. SN-593. Based on chemical structure, 5 type II polyketide synthase gene clusters were listed from the genome sequence of Streptomyces sp. SN-593. Among them, a candidate gene cluster was selected by comparing the gene organization with grincamycin, which is synthesized through an intermediate similar to kinanthraquinone. We initially utilized a BAC library for subcloning the kiq gene cluster, performed heterologous expression in Streptomyces lividans TK23, and identified the production of kinanthraquinone and kinanthraquinone B. We also found that heterologous expression of kiqA, which belongs to the DNA-binding response regulator OmpR family, dramatically enhanced the production of kinanthraquinones.

Biosynthesis of the uridine-derived nucleoside antibiotic A-94964: identification and characterization of the biosynthetic gene cluster provide insight into the biosynthetic pathway

2019 ◽  
Vol 17 (3) ◽  
pp. 461-466 ◽  
Author(s):  
Taro Shiraishi ◽  
Makoto Nishiyama ◽  
Tomohisa Kuzuyama
Keyword(s):  
Gene Cluster ◽  
In Silico ◽  
Biosynthetic Pathway ◽  
Gene Deletion ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Identification And Characterization ◽  
Insight Into

The biosynthetic pathway of the uridine-derived nucleoside antibiotic A-94964 was proposed via in silico analysis coupled with gene deletion experiments.

scholarly journals Cloning and Characterization of the Biosynthetic Gene Cluster for Tomaymycin, an SJG-136 Monomeric Analog

2009 ◽  
Vol 75 (9) ◽  
pp. 2958-2963 ◽  
Author(s):  
Wei Li ◽  
ShenChieh Chou ◽  
Ankush Khullar ◽  
Barbara Gerratana
Keyword(s):  
Cluster Analysis ◽  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Biosynthetic Gene Cluster ◽  
Gene Replacement ◽  
Biosynthetic Gene

ABSTRACT Tomaymycin produced by Streptomyces achromogenes is a naturally produced pyrrolobenzodiazepine (PBD). The biosynthetic gene cluster for tomaymycin was identified and sequenced. The gene cluster analysis reveals a novel biosynthetic pathway for the anthranilate moiety of PBDs. Gene replacement and chemical complementation studies were used to confirm the proposed biosynthetic pathway.

scholarly journals Biosynthetic engineering of the antifungal, anti-MRSA auroramycin

2019 ◽  
Author(s):  
Wan Lin Yeo ◽  
Elena Heng ◽  
Lee Ling Tan ◽  
Yi Wee Lim ◽  
Kuan Chieh Ching ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Genome Editing ◽  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Biosynthetic Gene Cluster ◽  
Combinatorial Biosynthesis ◽  
Biosynthetic Gene ◽  
Antifungal Activities ◽  
Biosynthetic Engineering

AbstractUsing an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseoporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, it also displays antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Six auroramycin analogs with variations in C-, N-methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.

scholarly journals Cloning and characterization of the goadsporin biosynthetic gene cluster from Streptomyces sp. TP-A0584

Microbiology ◽  
2005 ◽  
Vol 151 (12) ◽  
pp. 3923-3933 ◽  
Author(s):  
Hiroyasu Onaka ◽  
Mizuho Nakaho ◽  
Keiko Hayashi ◽  
Yasuhiro Igarashi ◽  
Tamotsu Furumai
Keyword(s):  
Gene Cluster ◽  
Signal Recognition Particle ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Gene Organization ◽  
Site Directed Mutagenesis ◽  
Biosynthetic Gene ◽  
Post Translational Modification ◽  
Subsequent Cyclization ◽  
Polypeptide Antibiotic

The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584. The cluster contains a structural gene, godA, and nine god (goadsporin) genes involved in post-translational modification, immunity and transcriptional regulation. Although the gene organization is similar to typical bacteriocin biosynthetic gene clusters, each goadsporin biosynthetic gene shows low homology to these genes. Goadsporin biosynthesis is initiated by the translation of godA, and the subsequent cyclization, dehydration and acetylation are probably catalysed by godD, godE, godF, godG and godH gene products. godI shows high similarity to the 54 kDa subunit of the signal recognition particle and plays an important role in goadsporin immunity. Furthermore, four goadsporin analogues were produced by site-directed mutagenesis of godA, suggesting that this biosynthesis machinery is used for the heterocyclization of peptides.

scholarly journals Biosynthetic Pathway for Mannopeptimycins, Lipoglycopeptide Antibiotics Active against Drug-Resistant Gram-Positive Pathogens

2006 ◽  
Vol 50 (6) ◽  
pp. 2167-2177 ◽  
Author(s):  
Nathan A. Magarvey ◽  
Brad Haltli ◽  
Min He ◽  
Michael Greenstein ◽  
John A. Hucul
Keyword(s):  
Amino Acid ◽  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Domain Analysis ◽  
Biosynthetic Gene Cluster ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Biosynthetic Gene ◽  
Peptide Synthetases ◽  
Multidrug Resistant Pathogens

ABSTRACT The mannopeptimycins are a novel class of lipoglycopeptide antibiotics active against multidrug-resistant pathogens with potential as clinically useful antibacterials. This report is the first to describe the biosynthesis of this novel class of mannosylated lipoglycopeptides. Included here are the cloning, sequencing, annotation, and manipulation of the mannopeptimycin biosynthetic gene cluster from Streptomyces hygroscopicus NRRL 30439. Encoded by genes within the mannopeptimycin biosynthetic gene cluster are enzymes responsible for the generation of the hexapeptide core (nonribosomal peptide synthetases [NRPS]) and tailoring reactions (mannosylation, isovalerylation, hydroxylation, and methylation). The NRPS system is noncanonical in that it has six modules utilizing only five amino acid-specific adenylation domains and it lacks a prototypical NRPS macrocyclizing thioesterase domain. Analysis of the mannopeptimycin gene cluster and its engineering has elucidated the mannopeptimycin biosynthetic pathway and provides the framework to make new and improved mannopeptimycins biosynthetically.

scholarly journals Unexpected distribution of the 4-formylaminooxyvinylglycine (FVG) biosynthetic pathway in Pseudomonas and beyond

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0247348
Author(s):  
Edward W. Davis ◽  
Rachel A. Okrent ◽  
Viola A. Manning ◽  
Kristin M. Trippe
Keyword(s):  
Mass Spectrometry ◽  
Gene Cluster ◽  
Biosynthetic Pathway ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Species Group ◽  
Biosynthetic Gene ◽  
Additional Gene ◽  
Genetic Potential ◽  
Lines Of Evidence

The biological herbicide and antibiotic 4-formylaminooxyvinylglycine (FVG) was originally isolated from several rhizosphere-associated strains of Pseudomonas fluorescens. Biosynthesis of FVG is dependent on the gvg biosynthetic gene cluster in P. fluorescens. In this investigation, we used comparative genomics to identify strains with the genetic potential to produce FVG due to presence of a gvg gene cluster. These strains primarily belong to two groups of Pseudomonas, P. fluorescens and P. syringae, however, a few strains with the gvg cluster were found outside of Pseudomonas. Mass spectrometry confirmed that all tested strains of the P. fluorescens species group produced FVG. However, P. syringae strains did not produce FVG under standard conditions. Several lines of evidence regarding the transmission of the gvg cluster including a robust phylogenetic analysis suggest that it was introduced multiple times through horizontal gene transfer within the Pseudomonas lineage as well as in select lineages of Thiomonas, Burkholderia and Pantoea. Together, these data broaden our understanding of the evolution and diversity of FVG biosynthesis. In the course of this investigation, additional gene clusters containing only a subset of the genes required to produce FVG were identified in a broad range of bacteria, including many non-pseudomonads.

Genome-based characterization of a plasmid-associated micrococcin P1 biosynthetic gene cluster and virulence factors in Mammaliicoccus sciuri IMDO-S72

2021 ◽  
Author(s):  
David Van der Veken ◽  
Charlie Hollanders ◽  
Marko Verce ◽  
Chris Michiels ◽  
Steven Ballet ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gene Cluster ◽  
Virulence Factors ◽  
Resistance Genes ◽  
De Novo ◽  
Antibiotic Resistance Genes ◽  
Mobile Genetic Elements ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Genetic Elements

Analysis of the de novo assembled genome of Mammaliicoccus sciuri IMDO-S72 revealed the genetically encoded machinery behind its earlier reported antibacterial phenotype and gave further insight into the repertoire of putative virulence factors of this recently reclassified species. A plasmid-encoded biosynthetic gene cluster was held responsible for the antimicrobial activity of M. sciuri IMDO-S72, comprising genes involved in thiopeptide production. The compound encoded by this gene cluster was structurally identified as micrococcin P1. Further examination of its genome highlighted the ubiquitous presence of innate virulence factors mainly involved in surface colonization. Determinants contributing to aggressive virulence were generally absent, with exception of a plasmid-associated ica cluster. The native antibiotic resistance genes sal (A) and mecA were detected within the genome, amongst others, but were not consistently linked with a resistant phenotype. While mobile genetic elements were identified within the genome, such as an untypeable SCC element, they proved to be generally free of virulence- and antibiotic-related genes. These results further suggest a commensal lifestyle of M. sciuri and indicate the association of antibiotic resistance determinants with mobile genetic elements, as an important factor in conferring antibiotic resistance, in addition to their unilateral annotation. Importance Mammaliicoccus sciuri has been put forward as an important carrier of virulence and antibiotic resistance genes, which can be transmitted to clinically important staphylococcal species such as Staphylococcus aureus . As a common inhabitant of mammal skin, this species is believed to have a predominant commensal lifestyle although it has been reported as an opportunistic pathogen in some cases. This study provides an extensive genome-wide description of its putative virulence potential taking into consideration the genomic context in which these genes appear, an aspect that is often overlooked during virulence analysis. Additional genome and biochemical analysis linked M. sciuri with the production of micrococcin P1, gaining further insight to which extent these biosynthetic gene cluster are distributed amongst different related species. The frequent plasmid-associated character hints that these traits can be horizontally transferred and might confer a competitive advantage to its recipient within its ecological niche.

scholarly journals Biosynthetic gene clusters and the evolution of fungal chemodiversity

2020 ◽  
Vol 37 (7) ◽  
pp. 868-878 ◽  
Author(s):  
Antonis Rokas ◽  
Matthew E. Mead ◽  
Jacob L. Steenwyk ◽  
Huzefa A. Raja ◽  
Nicholas H. Oberlies
Keyword(s):  
Gene Cluster ◽  
Horizontal Transfer ◽  
De Novo ◽  
Functional Divergence ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Biosynthetic Gene Clusters ◽  
Evolutionary Processes

This highlight synthesizes knowledge of the molecular evolutionary processes – functional divergence, horizontal transfer, and de novo assembly – that govern biosynthetic gene cluster diversification and the generation of chemodiversity in fungi.

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