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Updated: Jun 20, 2026

From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
Structure-Guided Discovery of Neuroprotective Kromycin-Type Macrolides from Streptomyces narbonensis sp
Ziheng Jing1,2, Bingya Jiang2, Weikang Li1
1College of Life Sciences, Institute of Life Science and Green Development and Hebei Innovation Center for Bioengineering and Biotechnology, Hebei University, Baoding 071002, China.
Abstract:
Six new kromycin-type macrolides, kromycins B-G (1-6), and with the known kromycin A (7), were isolated from Streptomyces narbonensis sp. CPCC 206470 guided by the Global Natural Products Social Molecular Networking (GNPS) analysis. Their structures were comprehensively established by extensive spectroscopic analyses, time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) comparison, and single-crystal X-ray diffraction analysis. These compounds represent a structurally distinct subclass of 14-membered macrolides. Compound 7 exhibited substantial neuroprotective activity by inhibiting Aβ42 aggregation and ameliorating oxidative stress and neuroinflammation in N2a neuronal cells. It enhanced antioxidant enzyme activities (SOD and CAT) and suppressed nitric oxide production. Genomic analysis identified a pikromycin-related biosynthetic gene cluster in the producing strain. This study expands the chemical diversity of kromycin-type natural products and highlights their potential as multitarget therapeutic agents for neurodegenerative diseases.
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