(27af) Novel Lasso Peptides Produced By Actinobacteria from the Atacama Desert | AIChE

(27af) Novel Lasso Peptides Produced By Actinobacteria from the Atacama Desert

Authors 

Martinez, I., Universidad de Chile
Asenjo, J., Centre for Biotechnology and Bioengineering
Natural products from bacteria are a great source of bioactive compounds. Extreme environments such as the Atacama Desert have a unique microbial biodiversity that had the potential to produce novel specialized metabolites1. Hence, the exploration of this habitat had led to the isolation of Actinobacteria that produce novel compounds, that can serve as therapeutic agents and help in the fight against antibiotic multi-resistance bacteria2. An interesting type of natural product are lasso peptides, they are ribosomally synthesized and are characterized by its lasso-structure3 and many of them have showed bioactivity4,5. The identification of lasso peptide biosynthetic gene clusters (BGCs) can be achieved through genome mining6. In this work, we performed first a screening of an Actinobacteria culture collection from the Atacama Desert, using degenerate primers specially designed to detect some of the genes present in the lasso peptide. This allowed us to select candidates for genome sequencing, and later identify the clusters through genome mining. The production of the novel lasso peptides was achieved by cloning the BGCs under a strong promoter into a Streptomyces heterologous host. Bioactivity studies of the lasso peptides showed that they have the potential to be used as therapeutic agents.

References:

  1. Bull, A. T. & Asenjo, J. A. Microbiology of hyper-arid environments: Recent insights from the Atacama Desert, Chile. Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology 103, 1173–1179 (2013).
  2. Razmilic, V., Castro, J. F., Marchant, F., Asenjo, J. A. & Andrews, B. Metabolic modelling and flux analysis of microorganisms from the Atacama Desert used in biotechnological processes. Antonie Van Leeuwenhoek 111, 1479–1491 (2018).
  3. Maksimov, M. O., Pan, S. J. & James Link, A. Lasso peptides: structure, function, biosynthesis, and engineering. Nat Prod Rep 29, 996 (2012).
  4. Gavrish, E. et al. Lassomycin, a ribosomally synthesized cyclic peptide, kills mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. Chem Biol 21, 509–518 (2014).
  5. Elsayed, S. S. et al. Chaxapeptin, a Lasso Peptide from Extremotolerant Streptomyces leeuwenhoekii Strain C58 from the Hyperarid Atacama Desert. J Org Chem 150924084048001 (2015) doi:10.1021/acs.joc.5b01878.
  6. Tietz, J. I. et al. A new genome-mining tool redefines the lasso peptide biosynthetic landscape. Nat Chem Biol 13, 470–478 (2017).