Identification and Heterologous Expression of the Albucidin Gene Cluster from the Marine Strain Streptomyces Albus Subsp. Chlorinus NRRL B-24108

Herbicides with new modes of action and safer toxicological and environmental profiles are needed to manage the evolution of weeds that are resistant to commercial herbicides. The unparalleled structural diversity of natural products makes these compounds a promising source for new herbicides. In 2009, a novel nucleoside phytotoxin, albucidin, with broad activity against grass and broadleaf weeds was isolated from a strain of Streptomyces albus subsp. chlorinus NRRL B-24108. Here, we report the identification and heterologous expression of the previously uncharacterized albucidin gene cluster. Through a series of gene inactivation experiments, a minimal set of albucidin biosynthetic genes was determined. Based on gene annotation and sequence homology, a model for albucidin biosynthesis was suggested. The presented results enable the construction of producer strains for a sustainable supply of albucidin for biological activity studies.

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Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108

Marine Drugs ◽

10.3390/md16110435 ◽

2018 ◽

Vol 16 (11) ◽

pp. 435 ◽

Cited By ~ 9

Author(s):

Marta Rodríguez Estévez ◽

Maksym Myronovskyi ◽

Nils Gummerlich ◽

Suvd Nadmid ◽

Andriy Luzhetskyy

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Gene Clusters ◽

Growth Conditions ◽

Pharmaceutical Drugs ◽

Gyra Gene ◽

Streptomyces Albus ◽

Potential Applications ◽

Resistant Mutants ◽

Marine Strain

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial pharmaceutical drugs. Here, we report the identification of the previously uncharacterized nybomycin gene cluster from the marine actinomycete Streptomyces albus subsp. chlorinus through its heterologous expression. Nybomycin has previously been reported to act against quinolone-resistant Staphylococcus aureus strains harboring a mutated gyrA gene but not against those with intact gyrA. The nybomycin-resistant mutants generated from quinolone-resistant mutants have been reported to be caused by a back-mutation in the gyrA gene that restores susceptibility to quinolones. On the basis of gene function assignment from bioinformatics analysis, we suggest a model for nybomycin biosynthesis.

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Bonsecamin: A New Cyclic Pentapeptide Discovered through Heterologous Expression of a Cryptic Gene Cluster

Microorganisms ◽

10.3390/microorganisms9081640 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1640

Author(s):

Constanze Lasch ◽

Marc Stierhof ◽

Marta Rodríguez Estévez ◽

Maksym Myronovskyi ◽

Josef Zapp ◽

...

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Gene Deletion ◽

Genome Mining ◽

Structural Complexity ◽

Bioinformatic Analysis ◽

Nrps Gene ◽

Minimal Set ◽

Streptomyces Albus ◽

Important Basis

The intriguing structural complexity of molecules produced by natural organisms is uncontested. Natural scaffolds serve as an important basis for the development of molecules with broad applications, e.g., therapeutics or agrochemicals. Research in recent decades has demonstrated that by means of classic metabolite extraction from microbes only a small portion of natural products can be accessed. The use of genome mining and heterologous expression approaches represents a promising way to discover new natural compounds. In this paper we report the discovery of a novel cyclic pentapeptide called bonsecamin through the heterologous expression of a cryptic NRPS gene cluster from Streptomyces albus ssp. chlorinus NRRL B-24108 in Streptomyces albus Del14. The new compound was successfully isolated and structurally characterized using NMR. The minimal set of genes required for bonsecamin production was determined through bioinformatic analysis and gene deletion experiments. A biosynthetic route leading to the production of bonsecamin is proposed in this paper.

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Direct cloning and heterologous expression of the salinomycin biosynthetic gene cluster from Streptomyces albus DSM41398 in Streptomyces coelicolor A3(2)

Scientific Reports ◽

10.1038/srep15081 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 36

Author(s):

Jia Yin ◽

Michael Hoffmann ◽

Xiaoying Bian ◽

Qiang Tu ◽

Fu Yan ◽

...

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Streptomyces Coelicolor ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Direct Cloning ◽

Streptomyces Albus

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Identification and heterologous expression of an isoquinolinequinone biosynthetic gene cluster from Streptomyces albus J1074

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2020.12.093 ◽

2021 ◽

Vol 540 ◽

pp. 51-55

Author(s):

Shumao Chai ◽

Mingming Cao ◽

Zhiyang Feng

Keyword(s):

Heterologous Expression ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Streptomyces Albus ◽

Streptomyces Albus J1074

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Dudomycins: New Secondary Metabolites Produced after Heterologous Expression of an Nrps Cluster from Streptomyces albus ssp. Chlorinus Nrrl B-24108

Microorganisms ◽

10.3390/microorganisms8111800 ◽

2020 ◽

Vol 8 (11) ◽

pp. 1800

Author(s):

Constanze Lasch ◽

Marc Stierhof ◽

Marta Rodríguez Estévez ◽

Maksym Myronovskyi ◽

Josef Zapp ◽

...

Keyword(s):

Natural Products ◽

Secondary Metabolites ◽

Heterologous Expression ◽

Treatment Options ◽

Gene Clusters ◽

Medical Applications ◽

Heterologous Host ◽

Minimal Set ◽

Wide Range ◽

Streptomyces Albus

Since the 1950s, natural products of bacterial origin were systematically developed to be used as drugs with a wide range of medical applications. The available treatment options for many diseases are still not satisfying, wherefore, the discovery of new structures has not lost any of its importance. Beyond the great variety of already isolated and characterized metabolites, Streptomycetes still harbor uninvestigated gene clusters whose products can be accessed using heterologous expression in host organisms. This works presents the discovery of a set of structurally novel secondary metabolites, dudomycins A to D, through the expression of a cryptic NRPS cluster from Streptomyces albus ssp. Chlorinus NRRL B-24108 in the heterologous host strain Streptomyces albus Del14. A minimal set of genes, required for the production of dudomycins, was defined through gene inactivation experiments. This paper also proposes a model for dudomycin biosynthesis.

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Direct Cloning, Genetic Engineering, and Heterologous Expression of the Syringolin Biosynthetic Gene Cluster inE. colithrough Red/ET Recombineering

ChemBioChem ◽

10.1002/cbic.201200310 ◽

2012 ◽

Vol 13 (13) ◽

pp. 1946-1952 ◽

Cited By ~ 52

Author(s):

Xiaoying Bian ◽

Fan Huang ◽

Francis A. Stewart ◽

Liqiu Xia ◽

Youming Zhang ◽

...

Keyword(s):

Genetic Engineering ◽

Heterologous Expression ◽

Gene Cluster ◽

Biosynthetic Gene Cluster ◽

Biosynthetic Gene ◽

Direct Cloning

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Discovery of Polycyclic Macrolide Shuangdaolides by Heterologous Expression of a Cryptic trans-AT PKS Gene Cluster

Organic Letters ◽

10.1021/acs.orglett.1c02589 ◽

2021 ◽

Author(s):

Yang Liu ◽

Haibo Zhou ◽

Qiyao Shen ◽

Guangzhi Dai ◽

Fu Yan ◽

...

Keyword(s):

Heterologous Expression ◽

Gene Cluster

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

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa082 ◽

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.

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