MDPI - Publisher of Open Access Journals

12 pages, 1087 KiB

Open AccessArticle

Miramides A–D: Identification of Detoxin-like Depsipeptides after Heterologous Expression of a Hybrid NRPS-PKS Gene Cluster from Streptomyces mirabilis Lu17588

by Constanze Paulus, Maksym Myronovskyi, Josef Zapp, Marta Rodríguez Estévez, Maria Lopatniuk, Birgit Rosenkränzer, Anja Palusczak and Andriy Luzhetskyy

Microorganisms 2022, 10(9), 1752; https://doi.org/10.3390/microorganisms10091752 - 30 Aug 2022

Cited by 5 | Viewed by 2463

Abstract

Natural products derived from plants, fungi or bacteria have been used for years in the medicine, agriculture and food industries as they exhibit a variety of beneficial properties, such as antibiotic, antifungal, anticancer, herbicidal and immunosuppressive activities. Compared to synthetic compounds, natural products possess a greater chemical diversity, which is a reason why they are profitable templates for developing pharmaceutical drug candidates and ongoing research on them is inevitable. Performing heterologous expression with unknown gene clusters is the preferred method to activate gene clusters that are not expressed in the wild-type strain under laboratory conditions; thus, this method offers a way to discover new interesting metabolites. Here, we report the gene cluster assembly of a hybrid NRPS-PKS gene cluster from Streptomyces mirabilis Lu17588, which was heterologously expressed in Streptomyces albus Del14. Four new compounds were produced by the obtained strain, which were named miramides A–D. Isolation and structure elucidation revealed similarity of the isolated compounds to the known depsipeptides rimosamides/detoxins. Full article

(This article belongs to the Special Issue Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics 3.0)

► Show Figures

Figure 1

16 pages, 2378 KiB

Open AccessArticle

A Promiscuous Halogenase for the Derivatization of Flavonoids

by Dominik Kolling, Marc Stierhof, Constanze Lasch, Maksym Myronovskyi and Andriy Luzhetskyy

Molecules 2021, 26(20), 6220; https://doi.org/10.3390/molecules26206220 - 14 Oct 2021

Cited by 5 | Viewed by 3633

Abstract

Halogenation often improves the bioactive properties of natural products and is used in pharmaceutical research for the generation of new potential drug leads. High regio- and stereospecificity, simple reaction conditions and straightforward downstream processing are the main advantages of halogenation using enzymatic biocatalysts compared to chemical synthetic approaches. The identification of new promiscuous halogenases for the modification of various natural products is of great interest in modern drug discovery. In this paper, we report the identification of a new promiscuous FAD-dependent halogenase, DklH, from Frankia alni ACN14a. The identified halogenase readily modifies various flavonoid compounds, including those with well-studied biological activities. This halogenase has been demonstrated to modify not only flavones and isoflavones, but also flavonols, flavanones and flavanonols. The structural requirements for DklH substrate recognition were determined using a feeding approach. The homology model of DklH and the mechanism of substrate recognition are also proposed in this paper. Full article

(This article belongs to the Special Issue Microbial Biotransformation of Natural Products)

► Show Figures

Figure 1

11 pages, 1164 KiB

Open AccessArticle

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

by Constanze Lasch, Marc Stierhof, Marta Rodríguez Estévez, Maksym Myronovskyi, Josef Zapp and Andriy Luzhetskyy

Microorganisms 2021, 9(8), 1640; https://doi.org/10.3390/microorganisms9081640 - 31 Jul 2021

Cited by 7 | Viewed by 3267

Abstract

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. Full article

(This article belongs to the Special Issue Microbial Non-Ribosomal Synthesis of Secondary Metabolites)

► Show Figures

Figure 1

11 pages, 993 KiB

Open AccessArticle

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

by Constanze Lasch, Marc Stierhof, Marta Rodríguez Estévez, Maksym Myronovskyi, Josef Zapp and Andriy Luzhetskyy

Microorganisms 2020, 8(11), 1800; https://doi.org/10.3390/microorganisms8111800 - 16 Nov 2020

Cited by 9 | Viewed by 2942

Abstract

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. Full article

(This article belongs to the Special Issue Natural Products from Streptomyces)

► Show Figures

Figure 1

11 pages, 946 KiB

Open AccessArticle

Loseolamycins: A Group of New Bioactive Alkylresorcinols Produced after Heterologous Expression of a Type III PKS from Micromonospora endolithica

by Constanze Lasch, Nils Gummerlich, Maksym Myronovskyi, Anja Palusczak, Josef Zapp and Andriy Luzhetskyy

Molecules 2020, 25(20), 4594; https://doi.org/10.3390/molecules25204594 - 9 Oct 2020

Cited by 14 | Viewed by 3269

Abstract

Natural products are a valuable source of biologically active compounds with potential applications in medicine and agriculture. Unprecedented scaffold diversity of natural products and biocatalysts from their biosynthetic pathways are of fundamental importance. Heterologous expression and refactoring of natural product biosynthetic pathways are generally regarded as a promising approach to discover new secondary metabolites of microbial origin. Here, we present the identification of a new group of alkylresorcinols after transcriptional activation and heterologous expression of the type III polyketide synthase of Micromonospora endolithica. The most abundant compounds loseolamycins A1 and A2 have been purified and their structures were elucidated by NMR. Loseolamycins contain an unusual branched hydroxylated aliphatic chain which is provided by the host metabolism and is incorporated as a starter fatty acid unit. The isolated loseolamycins show activity against gram-positive bacteria and inhibit the growth of the monocot weed Agrostis stolonifera in a germination assay. The biosynthetic pathway leading to the production of loseolamycins is proposed in this paper. Full article

(This article belongs to the Special Issue Microbial Natural Products in The Era of Genome- And Metabolome-Mining)

► Show Figures

Figure 1

10 pages, 1061 KiB

Open AccessArticle

Identification of a Biosynthetic Gene Cluster Responsible for the Production of a New Pyrrolopyrimidine Natural Product—Huimycin

by Hui Shuai, Maksym Myronovskyi, Suvd Nadmid and Andriy Luzhetskyy

Biomolecules 2020, 10(7), 1074; https://doi.org/10.3390/biom10071074 - 18 Jul 2020

Cited by 15 | Viewed by 3987

Abstract

Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain Kutzneria albida DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Streptomyces albus Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper. Full article

(This article belongs to the Section Natural and Bio-derived Molecules)

► Show Figures

Figure 1

11 pages, 835 KiB

Open AccessArticle

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

by Maksym Myronovskyi, Birgit Rosenkränzer, Marc Stierhof, Lutz Petzke, Tobias Seiser and Andriy Luzhetskyy

Microorganisms 2020, 8(2), 237; https://doi.org/10.3390/microorganisms8020237 - 10 Feb 2020

Cited by 17 | Viewed by 3941

Abstract

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. Full article

(This article belongs to the Special Issue Actinobacteria and Myxobacteria—Important Resources for Novel Antibiotics 2.0)

► Show Figures

Figure 1

Search Results (7)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (7)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI