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Polyoxin and nikkomycin are naturally occurring peptidyl nucleoside antibiotics with potent antifungal bioactivity. Both exhibit similar structural features, having a nucleoside skeleton and one or two peptidyl moieties. Combining the refactoring of the polyoxin producer Streptomyces aureochromogenes with import of the hydroxypyridylhomothreonine pathway of nikkomycin allows the targeted production of three designer nucleoside antibiotics designated as nikkoxin E, F, and G. These structures were determined by NMR and/or high resolution mass spectrometry. Remarkably, the introduction of an extra copy of the nikS gene encoding an ATP-dependent ligase significantly enhanced the production of the designer antibiotics. Moreover, all three nikkoxins displayed improved bioactivity against several pathogenic fungi as compared with the naturally-occurring antibiotics. These data provide a feasible model for high efficiency generation of nucleoside antibiotics related to polyoxins and nikkomycins in a polyoxin cell factory via synthetic biology strategy

nikkomycin, Streptomyces aureochromogenes, designer nucleoside antibiotics, peptidyl nucleoside antibiotics, synthetic biology, the polyoxin producer

NCBI PubMed ID: 25827606
Publication DOI: 10.1002/bit.25594
Journal NLM ID: 7502021
Publisher: New York: Wiley-VCH
Correspondence: Chen W
Institutions: Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China, State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China
Methods: biological assays, HPLC, UV, LC-MS, cell growth, antifungal activity test

myo-Inositol, a cyclitol (cyclohexanepolyol) which is classified as a type of carbohydrates, occurs widely in nature and is known as a constituent of a secondary messenger in cells which stimulates the release of calcium from storage site. It is produced in large quantities from plants (rice bran and corn-steep liquors) by food industry. In spite of its abundance in nature and ready availability, myo-inositol has not been utilized widely as the starting material for the synthesis of natural products other than cyclitol derivatives. Given that regioselective ring cleavage of the cyclohexane ring in optically active and functionalized cyclitol derivatives is possible, myo-inositol is expected to be a potential precursor with stereochemical diversity for novel chiral building blocks in the synthesis of various natural products. In this article, preparation and optical resolution of protected myo-inositol derivatives are shortly reviewed. Overview of regioselective ring cleavages of cyclohexanones derived from cyclitols by way of the Baeyer-Villiger reaction, and the syntheses of some natural products based on the methodologies which involve the ring cleavage reaction of myo-inositol, is also described

myo-inositol, cyclitols, optical resolution, regioselective ring cleavage, chiral building block, Baeyer-Villiger reaction

Publication DOI: 10.5059/yukigoseikyokaishi.58.642
Journal NLM ID: 21720350R
Publisher: Tokyo
Institutions: Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Tokyo, Japan

nikkomycin, Streptomyces aureochromogenes, designer nucleoside antibiotics, peptidyl nucleoside antibiotics, synthetic biology, the polyoxin producer