Self-resistance-gene-guided, high-throughput automated genome mining of bioactive natural products from Streptomyces.

Cell Syst

Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA. Electronic address:

Published: March 2025

Natural products (NPs) from bacteria, fungi, and plants are a vital source of drug leads, with Streptomyces species being particularly significant due to their capability of producing diverse bioactive compounds. Here, we present a fully automated, scalable, high-throughput platform for discovering bioactive NPs in Streptomyces (FAST-NPS). This platform integrates computational biosynthetic gene cluster (BGC) prediction and prioritization guided by self-resistance genes, automated cloning and heterologous expression, high-throughput fermentation, and product extraction. As a proof of concept, we cloned 105 BGCs (10-100 kb) from 11 Streptomyces strains with a 95% success rate. Heterologous expression in Streptomyces lividans TK24 led to the detection of 23 NPs, including 8 with antibacterial or antitumor bioactivities from 5 BGCs. This work highlights the potential of FAST-NPS to accelerate bioactive NP discovery for biomedical and biotechnological applications. A record of this paper's transparent peer review process is included in the supplemental information.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cels.2025.101237DOI Listing

Publication Analysis

Top Keywords

natural products
8
heterologous expression
8
streptomyces
5
self-resistance-gene-guided high-throughput
4
high-throughput automated
4
automated genome
4
genome mining
4
bioactive
4
mining bioactive
4
bioactive natural
4

Similar Publications

Multidrug resistance (MDR) infectious wounds are a major concern due to drug resistance, leading to increased patient morbidity. Lichenysin (LCN), a lipopeptide and biosurfactant obtained from certain strains of , has demonstrated an excellent antimicrobial property. The present study focuses on the fabrication and comprehensive evaluation of LCN-incorporated poly(vinyl alcohol) (PVA)/polycaprolactone (PCL)-based nanofiber scaffolds using an electrospinning technique as a potential wound healing biomaterial for the treatment of MDR infectious wounds in diabetic rats.

View Article and Find Full Text PDF

Inducible regulating homologous recombination enables precise genome editing in Pichia pastoris without perturbing cellular fitness.

Trends Biotechnol

March 2025

Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, PR China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, PR China; Dalian Key Laboratory of Energy Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, PR China. Electronic address:

The methylotrophic yeast Pichia pastoris (also known as Komagataella pastoris) is an ideal host for producing proteins and natural products. Enhancing homologous recombination (HR) is helpful for improving the precision of genome editing, but results in stress to cellular fitness and is harmful for industrial applications. To overcome these challenges, we developed a tetracycline repressor protein (TetR)/tetO2 inducible system to dynamically regulate the HR-related gene RAD52 in P.

View Article and Find Full Text PDF

Herein we report the enantioselective synthesis of 3-allyl-3-hydroxyoxindoles, a core scaffold in a wide range of bioactive molecules, using a Lewis-base catalyst and readily abundant and inexpensive allyltrichlorosilane. This transition-metal-free protocol employs relatively low catalyst loadings of a privileged bispyrrolidine-type scaffold to achieve high yields and enantioselectivities (up to 98% yield and 98:2 er). The total syntheses of the natural products (-)-flustraminol B and (-)-chimonamidine were also successfully carried out using our newly developed method as a key step, highlighting the potential of this method for the efficient and precise synthesis of complex natural products.

View Article and Find Full Text PDF

Background: Herbal medicines and their preparations play a significant role in healthcare systems, yet concerns remain about their quality consistency. Chemical fingerprinting and multi-component quantitative analysis are the commonly used analytical methods and are widely applied in the quality analysis of herbal medicines. The study uses Gegen Qinlian tablets (GQTs) as a case to propose a comprehensive quality consistency evaluation system.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!