Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture

Abstract

Actinomycetes are a rich source of bioactive natural products important for novel drug leads. Recent genome mining approaches have revealed an enormous number of secondary metabolite biosynthetic gene clusters (smBGCs) in actinomycetes. However, under standard laboratory culture conditions, many smBGCs are silent or cryptic. To activate these dormant smBGCs, several approaches, including culture-based or genetic engineering-based strategies, have been developed. Above all, coculture is a promising approach to induce novel secondary metabolite production from actinomycetes by mimicking an ecological habitat where cryptic smBGCs may be activated. In this review, we introduce coculture studies that aim to expand the chemical diversity of actinomycetes, by categorizing the cases by the type of coculture partner. Furthermore, we discuss the current challenges that need to be overcome to support the elicitation of novel bioactive compounds from actinomycetes.

Fungal Endophytes: A Potential Source of Antibacterial Compounds

“…In co-culture technique real-time bioactivity screening can also be measured by the growth of pathogen as co-culture [218]. Recently, Kim et al [237] reviewed the co-culture interactions of fungi with various actinomycetes for induction of silent biosynthetic gene clusters and reported upregulation and production of novel antibiotics and bioactive compounds. Co-culturing of microbes provides the habitat type environment to producers and helps to promote silent BGCs by producing signal molecules.…”

“Microbial Wars” in a Stirred Tank Bioreactor: Investigating the Co-Cultures of Streptomyces rimosus and Aspergillus terreus, Filamentous Microorganisms Equipped With a Rich Arsenal of Secondary Metabolites

“…No less important is the fungal genus Aspergillus , which is well-recognized for its biosynthetic capabilities ( Cairns et al, 2018 ; Romsdahl and Wang, 2019 ; Caesar et al, 2020 ). In the previous studies, the members of the Aspergillus and Streptomyces genera were successfully co-cultured to induce the formation of secondary metabolites (reviewed by Kim et al, 2021 ). However, we are not aware of any previous “ Streptomyces vs. Aspergillus ” reports regarding the stirred tank bioreactor-based analyses of the secondary metabolic profiles and the related bioprocess-related kinetic data.…”

Synthetic biology approaches to actinomycete strain improvement

“…Novel actinomycete strains, producing new compounds of interest with the potential of becoming industrial products, such as pharmaceuticals, crop-protecting agents or food additives are identified regularly (Onaka 2017 ; Kim et al . 2021 ). Initially, these novel strains of interest are not immediately used at an industrial scale, as their use presents several challenges due to a limited understanding of the strain and/or the product.…”