Heterologous cross-expression of oxygenase and glycosyltransferase genes in streptomycetes, producing angucyclic antibiotics

The heterologous expression of oxygenase genes urdM, ovmOIII, lanM2, lndZ5 and glycosyltransferase gene urdGT2 in different angucycline producers of genus Streptomyces has been carried out. The introduction of genes urdM, lanM2 and urdGT2 results in the accumulation of new glycosylated compounds in several strains under investigation. A number of processed recombinant strains display streptomycin sensitivity and decrease in total antibacterial activity. The obtained data is an evidence of changes in antibiotics production, resulting from post polyketide synthase (postPKS) tailoring gene expression across streptomycete strains. Our study demonstrates the potential of post PKS tailoring genes for generation of novel bioactive metabolites.Здійснено гетерологічну експресію генів оксигеназ urdM, ovmOIII, lanM2, lndZ5 та глікозилтрансферази urdGT2 у різних видів продуцентів ангуциклінів з роду Streptomyces. Введення генів urdM, lanM2 та urdGT2 у деякі з досліджуваних штамів зумовлює накопичення ними нових глікозильованих сполук. Виявлено виникнення чутливості до стрептоміцину та різке зниження загальної антибактерійної активності у деяких із одержаних рекомбінантних штамів. Отримані дані є свідченням модифікації продукції антибіотиків, яка є наслідком експресії генів постполікетидного синтезу (пост-ПКС) у штамах стрептоміцетів. Наші дослідження демонструють потенціал генів пост-ПКС у створенні нових біологічно активних метаболітів.Проведена гетерологическая экспрессия генов оксигеназ urdM, ovmOIII, lanM2, lndZ5 и гликозилтрансферазы urdGT2 в разных видах продуцентов ангуциклинов из рода Streptomyces. Введение генов urdM, lanM2 и urdGT2 в некоторые из исследуемых штаммов обусловливает накопление ими новых гликозилированных соединений. Обнаружено появление чувствительности к стрептомицину и резкое снижение общей антибактериальной активности у некоторых из полученных рекомбинантных штаммов. Представленные данные свидетельствуют о модификации продукции антибиотиков, которая является следствием экспрессии генов пост-поликетидного синтеза (пост-ПКС) в штаммах стрептомицетов. Наши исследования демонстрируют потенциал генов пост-ПКС в создании новых биологически активных метаболитов

Chemical Approaches To Perturb, Profile, and Perceive Glycans

Glycosylation is an essential form of post-translational modification that regulates intracellular and extracellular processes. Regrettably, conventional biochemical and genetic methods often fall short for the study of glycans, because their structures are often not precisely defined at the genetic level. To address this deficiency, chemists have developed technologies to perturb glycan biosynthesis, profile their presentation at the systems level, and perceive their spatial distribution. These tools have identified potential disease biomarkers and ways to monitor dynamic changes to the glycome in living organisms. Still, glycosylation remains the underexplored frontier of many biological systems. In this Account, we focus on research in our laboratory that seeks to transform the study of glycan function from a challenge to routine practice

Minimum Information about a Biosynthetic Gene cluster

A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.Chemistry and Chemical Biolog

Secondary Metabolome and Transcriptome of Streptomyces albus J1074 in Liquid Medium SG2

Koshla OT, Rokytskyy IV, Ostash IS, et al. Secondary Metabolome and Transcriptome of Streptomyces albus J1074 in Liquid Medium SG2. CYTOLOGY AND GENETICS. 2019;53(1):1-7.Streptomyces albus J1074 is one of the most popular chassis for heterologous expression of actino-bacterial biosynthetic gene clusters (BGCs). Considerable efforts are invested into understanding all the physiological and genetic aspects of secondary metabolism of J1074 in order to maximize the expression of heterologous BGCs. It has to be noted that the J1074 genome itself is home to numerous (> 20) BGCs, whose expression varies widely. Therefore, the identification of the factors limiting the expression of J1074 BGCs might help improve this strain for heterologous expression purposes. As first steps towards this goal, herein we describe the secondary metabolome of J1074 in liquid medium SG2, previously shown by us to support the production of antibacterial and antifungal compounds. We compare the results of metabolomic studies with the transcriptome of J1074 in SG2 after 60 h of growth. Results of our studies are discussed in the context of current knowledge on the J1074 transcriptome and metabolome data