Dataset Information

Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator.

ABSTRACT: Humidimycin (MDN-0010) is a ribosomally synthesized and post-translationally modified peptide (RiPP) belonging to class I lasso peptides, and is structurally related to siamycins, which have been shown to have strong antimicrobial activities against Gram-positive bacteria and to possess anti-HIV activity. Humidimycin was isolated from the strain Streptomyces humidus CA-100629, and was shown to synergize the activity of the fungal cell wall inhibitor caspofungin. In this work, the biosynthetic gene cluster of humidimycin was identified by genome mining of S. humidus CA-100629, cloned by Gibson assembly, and heterologously expressed.

SUBMITTER: Sanchez-Hidalgo M

PROVIDER: S-EPMC7168211 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator.

Sánchez-Hidalgo Marina M Martín Jesús J Genilloud Olga O

Antibiotics (Basel, Switzerland) 20200207 2

Humidimycin (MDN-0010) is a ribosomally synthesized and post-translationally modified peptide (RiPP) belonging to class I lasso peptides, and is structurally related to siamycins, which have been shown to have strong antimicrobial activities against Gram-positive bacteria and to possess anti-HIV activity. Humidimycin was isolated from the strain <i>Streptomyces humidus</i> CA-100629, and was shown to synergize the activity of the fungal cell wall inhibitor caspofungin. In this work, the biosynth ...[more]

PMID: 32046042

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Project description:Analysis of the genome sequence of Streptomyces leeuwenhoekii C34T identified biosynthetic gene clusters (BGCs) for three different lasso peptides (Lp1, Lp2, and Lp3) which were not known to be made by the strain. Lasso peptides represent relatively new members of the RiPP (ribosomally synthesized and posttranslationally modified peptides) family of natural products and have not been extensively studied. Lp3, whose production could be detected in culture supernatants from S. leeuwenhoekii C34T and after heterologous expression of its BGC in Streptomyces coelicolor, is identical to the previously characterized chaxapeptin. Lp1, whose production could not be detected or achieved heterologously, appears to be identical to a recently identified member of the citrulassin family of lasso peptides. Since production of Lp2 by S. leeuwenhoekii C34T was not observed, its BGC was also expressed in S. coelicolor The lasso peptide was isolated and its structure confirmed by mass spectrometry and nuclear magnetic resonance analyses, revealing a novel structure that appears to represent a new family of lasso peptides.IMPORTANCE Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RiPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RiPPs.

Dataset Information

Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator.

Publications

Identification and Heterologous Expression of the Biosynthetic Gene Cluster Encoding the Lasso Peptide Humidimycin, a Caspofungin Activity Potentiator.

Similar Datasets

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