Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in Trichoderma harzianum t-22

2021 ◽  
Vol 19 (9) ◽  
pp. 1985-1990
Author(s):  
Yiguang Zhu ◽  
Junfeng Wang ◽  
Pengyun Mou ◽  
Yan Yan ◽  
Mengbin Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Double Bond ◽  
Gene Cluster ◽  
Trichoderma Harzianum ◽  
Bond Formation ◽  
Genome Mining ◽  
Exocyclic Double Bond ◽  
Encoding Gene

The gene cluster of trihazones was identified from Trichoderma harzianum t-22 and heterologously activated in Aspergillus nidualns. The α-KG dependent dioxygenase ThnC was confirmed to catalyze exocyclic double bond formation.

scholarly journals Genome Mining and Metabolic Profiling Uncover Polycyclic Tetramate Macrolactams from Streptomyces koyangensis SCSIO 5802

Marine Drugs ◽  
2021 ◽  
Vol 19 (8) ◽  
pp. 440
Author(s):  
Wenjuan Ding ◽  
Jiajia Tu ◽  
Huaran Zhang ◽  
Xiaoyi Wei ◽  
Jianhua Ju ◽  
...  
Keyword(s):  
Natural Products ◽  
Gene Cluster ◽  
Metabolic Profiling ◽  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Open Reading Frames ◽  
Bioactive Metabolites ◽  
Bioinformatics Analyses ◽  
Reading Frames

We have previously shown deep-sea-derived Streptomyces koyangensis SCSIO 5802 to produce two types of active secondary metabolites, abyssomicins and candicidins. Here, we report the complete genome sequence of S. koyangensis SCSIO 5802 employing bioinformatics to highlight its potential to produce at least 21 categories of natural products. In order to mine novel natural products, the production of two polycyclic tetramate macrolactams (PTMs), the known 10-epi-HSAF (1) and a new compound, koyanamide A (2), was stimulated via inactivation of the abyssomicin and candicidin biosynthetic machineries. Detailed bioinformatics analyses revealed a PKS/NRPS gene cluster, containing 6 open reading frames (ORFs) and spanning ~16 kb of contiguous genomic DNA, as the putative PTM biosynthetic gene cluster (BGC) (termed herein sko). We furthermore demonstrate, via gene disruption experiments, that the sko cluster encodes the biosynthesis of 10-epi-HSAF and koyanamide A. Finally, we propose a plausible biosynthetic pathway to 10-epi-HSAF and koyanamide A. In total, this study demonstrates an effective approach to cryptic BGC activation enabling the discovery of new bioactive metabolites; genome mining and metabolic profiling methods play key roles in this strategy.

scholarly journals A Pseudoalteromonas clade with remarkable biosynthetic potential

2021 ◽  
Author(s):  
Rocky Chau ◽  
Leanne A. Pearson ◽  
Jesse Cain ◽  
John A. Kalaitzis ◽  
Brett A. Neilan
Keyword(s):  
Natural Products ◽  
Gene Cluster ◽  
Genome Mining ◽  
Gene Clusters ◽  
Average Density ◽  
Biologically Active ◽  
Biosynthesis Gene Cluster ◽  
Diverse Range ◽  
Siderophore Biosynthesis ◽  
Biosynthesis Gene

Pseudoalteromonas species produce a diverse range of biologically active compounds, including those biosynthesized by non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here we report the biochemical and genomic analysis of Pseudoalteromonas sp. HM-SA03, isolated from the blue-ringed octopus, Hapalochalaena sp. Genome mining for secondary metabolite pathways revealed seven putative NRPS/PKS biosynthesis gene clusters, including those for the biosynthesis of alterochromides, pseudoalterobactins, alteramides and four hitherto novel compounds. Among these was a novel siderophore biosynthesis gene cluster with unprecedented architecture (NRPS-PKS-NRPS-PKS-NRPS-PKS-NRPS). Alterochromide production in HM-SA03 was also confirmed by liquid chromatography-mass spectrometry. An investigation of the biosynthetic potential of 42 publicly available Pseudoalteromonas genomes indicated that some of these gene clusters are distributed throughout the genus. Through phylogenetic analysis, a particular subset of strains formed a clade with extraordinary biosynthetic potential, with an average density of ten biosynthesis gene clusters per genome. In contrast, the majority of Pseudoalteromonas strains outside this clade contained an average of three clusters encoding complex biosynthesis. These results highlight the under-explored potential of Pseudoalteromonas as a source of new natural products. Importance This study demonstrates that the Pseudoalteromonas strain, HM-SA03, isolated from the venomous blue-ringed octopus, Hapalochalaena sp., is a biosynthetically talented organism, capable of producing alterochromides and potentially six other specialized metabolites. We have identified a pseudoalterobactin biosynthesis gene cluster and proposed a pathway for the production of the associated siderophore. A novel siderophore biosynthesis gene cluster with unprecedented architecture was also identified in the HM-SA03 genome. Finally, we have demonstrated that HM-SA03 belongs to a phylogenetic clade of strains with extraordinary biosynthetic potential. While our results do not support a role of HM-SA03 in Hapalochalaena sp. venom (tetrodotoxin) production, they emphasize the untapped potential of Pseudoalteromonas as a source of novel natural products.

scholarly journals Genome Mining and Heterologous Expression of Lipoamides and Amicoumacins From Compost-Associated Bacillus subtilis fmb60

2021 ◽  
Author(s):  
jie yang ◽  
Qingzheng Zhu ◽  
Feng Xu ◽  
Ming Yang ◽  
Hechao Du ◽  
...  
Keyword(s):  
Natural Products ◽  
Bacillus Subtilis ◽  
Secondary Metabolites ◽  
Heterologous Expression ◽  
Gene Cluster ◽  
Broad Spectrum ◽  
Genome Mining ◽  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
First Time

Abstract: Bacillus subtilis fmb60, which has broad-spectrum antimicrobial activities was isolated from plant straw compost. A hybrid NRPS/PKS cluster was screened from the genome. Sixteen secondary metabolites produced by the gene cluster were isolated and identified using LC-HRMS and NMR. Three lipoamides D–F (1-3) and two amicoumacin derivatives, amicoumacins D, E (4, 5), were identified, and are reported here for the first time. Lipoamides D–F exhibited strong antibacterial activities against harmful foodborne bacteria, with the MIC ranging from 6.25 to 25 µg/mL. Amicoumacin E scavenged 38.8% of ABTS+ radicals at 1 mg/mL. Direct cloning and heterologous expression of the NRPS/PKS and ace gene cluster identified its importance for the biosynthesis of amicoumacins. This study demonstrated that there is a high potential for biocontrol utilization of B. subtilis fmb60, and genome mining for clusters of secondary metabolites of B. subtilis fmb60 has revealed a greater biosynthetic potential for the production of novel natural products than previously anticipated.

Discovery and Heterologous Production of Sarubicins and Quinazolinone C-Glycosides with Protecting Activity for Cardiomyocytes

2021 ◽  
Author(s):  
Mingming Yu ◽  
Jianying Luo ◽  
Dan Luo ◽  
Qiang He ◽  
Yijun Yan ◽  
...  
Keyword(s):  
Natural Products ◽  
Gene Cluster ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Heterologous Production ◽  
Biosynthetic Gene ◽  
Pharmaceutical Agents

Glycosylated natural products and their derivatives are important pharmaceutical agents. Genome mining of C-glycosylated metabolites biosynthetic gene cluster (BGC) from a soil-derived Streptomyces led to the isolation of sarubicins A...

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