Impact of Streptomyces and their specialized metabolites

The microbial world, having evolved over billions of years through numerous mass extinction events and a vast array of climatic conditions, is a testament to life’s resilience and adaptability on Earth. Microorganisms have played a pivotal role in shaping life as we know it, contributing significantly to the evolution and sustenance of complex ecosystems. Despite their long-standing presence, our understanding of these microscopic entities has only deepened over the past 400 years, revealing their crucial role in maintaining Earth’s ecological balance.

In the realm of biotechnology, there has been remarkable progress in isolating specific microorganisms from natural environments and harnessing their potential for societal benefit. However, much remains unknown about the evolutionary reasons behind the maintenance of certain enzymes in microbial genomes and the roles these enzymes and their biosynthetic products play within their native multi-species ecosystems. Understanding the intricate dynamics of these microbial communities and the factors influencing them is key to comprehending the potential impacts of climate change on these ecosystems and devising strategies to prevent soil desertification and erosion.

This PhD thesis delves into the study of Streptomyces spp., a genus ubiquitously present in soils worldwide and known for its prolific production of bioactive compounds. As part of the Center for Microbial Secondary Metabolites (CeMiSt), this project focuses on strains isolated from a specific sampling site shared with other research groups of the center. The primary aim is to gain a deeper understanding
of these strains and their potential for experimental applications in community dy-namics studies. The role of secondary metabolites in nature, particularly the effects that antibiotics have at sub-inhibitory concentrations, remains largely unexplored, warranting thorough investigation that are focus of many research groups around the world.

This research contributes to our understanding of the molecules produced by Streptomyces spp., particularly focusing on azodyrecins, a class of azoxy compounds. Despite the widespread occurrence of azoxy biosynthetic gene clusters in Streptomyces genomes, only a few azoxy metabolites have been characterized to date. The unique structure of azodyrecins and the prevalence of their biosynthetic genes suggest a crucial, yet undiscovered, ecological role.

In addition to advancing our knowledge about azoxy molecule biosynthesis in Streptomyces spp., we identified novel pepticinnamin analogues, discovered a novel isoquinolinequinone terpenoid, maramycin, that is synthesised through cross talk of a rare bifunctional enzyme and host biosynthetic machinery, and successfully established CRISPR base editing in Streptomyces mirabilis P8-A2, demonstrating its efficacy
as a host for genome engineering. These findings not only enhance our understanding of microbial metabolic pathways but also pave the way for future biotechnological innovations and understanding their roles in shaping their natural environment.