School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand.
mSystems. 2023 Apr 27;8(2):e0103022. doi: 10.1128/msystems.01030-22. Epub 2023 Feb 7.
Actinomycetes are prolific producers of industrially valuable and medically important compounds. Historically, the most efficient method of obtaining compounds has been bioactivity-guided isolation and characterization of drug-like molecules from culturable soil actinomycetes. Unfortunately, this pipeline has been met with an increasing number of rediscoveries, to the point where it is no longer considered an attractive approach for drug discovery. To address this challenge and to continue finding new compounds, researchers have increasingly focused on alternative environmental niches and screening methods. Here, we report the genetic investigation of actinomycetes from an underexplored source, New Zealand lichens. In this work, we obtain draft genome sequences for 322 lichen-associated actinomycetes. We then explore this genetic resource with an emphasis on biosynthetic potential. By enumerating biosynthetic gene clusters (BGCs) in our data sets and comparing these to various reference collections, we demonstrate that actinomycetes sourced from New Zealand lichens have the genetic capacity to produce large numbers of natural products, many of which are expected to be broadly different from those identified in previous efforts predominantly based on soil samples. Our data shed light on the actinomycete assemblage in New Zealand lichens and demonstrate that lichen-sourced actinobacteria could serve as reservoirs for discovering new secondary metabolites. Lichens are home to complex and distinctive microbial cohorts that have not been extensively explored for the ability to produce novel secondary metabolites. Here, we isolate and obtain genome sequence data for 322 actinomycetes from New Zealand lichens. In doing so, we delineate at least 85 potentially undescribed species, and show that lichen associated actinomycetes have the potential to yield many new secondary metabolites, and as such, might serve as a productive starting point for drug discovery efforts.
放线菌是具有工业价值和医学重要性的化合物的丰富生产者。历史上,获得化合物的最有效方法是从可培养土壤放线菌中分离和鉴定具有药物特性的分子的生物活性指导。不幸的是,这种方法已经遇到了越来越多的重复发现,以至于它不再被认为是一种有吸引力的药物发现方法。为了解决这一挑战并继续寻找新的化合物,研究人员越来越关注替代的环境小生境和筛选方法。在这里,我们报告了对一个未充分探索的来源——新西兰地衣中的放线菌的遗传研究。在这项工作中,我们获得了 322 株地衣相关放线菌的草图基因组序列。然后,我们通过重点研究生物合成潜力来探索这一遗传资源。通过枚举我们数据集和各种参考集集中的生物合成基因簇(BGC),我们证明了从新西兰地衣中获得的放线菌具有产生大量天然产物的遗传能力,其中许多预计与以前主要基于土壤样本的努力中鉴定的产物有很大的不同。我们的数据阐明了新西兰地衣中放线菌的组合,并证明了地衣来源的放线菌可以作为发现新次生代谢物的资源。地衣是复杂而独特的微生物群落的家园,这些微生物群落的产生新型次生代谢物的能力尚未得到广泛探索。在这里,我们从新西兰地衣中分离并获得了 322 株放线菌的基因组序列数据。在这样做的过程中,我们至少划定了 85 种可能未被描述的物种,并表明与地衣相关的放线菌具有产生许多新次生代谢物的潜力,因此,可能成为药物发现努力的一个富有成效的起点。