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

Marina Sánchez-Hidalgo; Jesús Martín; Olga Genilloud

doi:10.3390/antibiotics9020067

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

Antibiotics (Basel). 2020 Feb 7;9(2):67. doi: 10.3390/antibiotics9020067.

Authors

Marina Sánchez-Hidalgo¹, Jesús Martín¹, Olga Genilloud¹

Affiliation

¹ Fundación MEDINA, Avenida del Conocimiento 34, 18016 Granada, Spain.

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.

Keywords: Gibson assembly; Humidimycin; MDN-0010; RiPP; Streptomyces humidus; biosynthetic gene cluster; genome mining; heterologous expression; lasso peptide.