Abstract
The benzopyran compound obtained by cultivating a mangrove-derived strain, Streptomyces xiamenensis strain 318, shows multiple biological effects, including anti-fibrotic and anti-hypertrophic scar properties. To increase the diversity in the structures of the available benzopyrans, by means of biosynthesis, the strain was screened for spontaneous rifampicin resistance (Rif), and a mutated rpsL gene to confer streptomycin resistance (Str), was introduced into the S. xiamenensis strain M1-94P that originated from deep-sea sediments. Two new benzopyran derivatives, named xiamenmycin C (1) and D (2), were isolated from the crude extracts of a selected Str-Rif double mutant (M6) of M1-94P. The structures of 1 and 2 were identified by analyzing extensive spectroscopic data. Compounds 1 and 2 both inhibit the proliferation of human lung fibroblasts (WI26), and 1 exhibits better anti-fibrotic activity than xiamenmycin. Our study presents the novel bioactive compounds isolated from S. xiamenensis mutant strain M6 constructed by ribosome engineering, which could be a useful approach in the discovery of new anti-fibrotic compounds.
Highlights
During daily urban life, a causal relationship between the elevated urban air pollution and an increased severity of airway diseases, including lung fibrosis and lung cancers, has been supported by epidemiological and toxicological research [1,2]
It was reported that the introduction of multiple drug resistant mutations had the cumulative effect of increasing the production of secondary metabolites, which led to a dramatic increase in the production of the bioactive compounds
The benzopyran compound xiamenmycin can be obtained through the cultivation of a mangrove-derived strain of Streptomyces xiamenensis, strain 318, and it has multiple anti-fibrotic effects
Summary
A causal relationship between the elevated urban air pollution and an increased severity of airway diseases, including lung fibrosis and lung cancers, has been supported by epidemiological and toxicological research [1,2]. A result of chronic inflammatory reactions induced by a variety of stimuli, has recently garnered increasing attention [3]. Fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis are threatening the public health [3]. The NdeI-EcoRV fragments containing mutated rpsL genes were excised and inserted into the same sites of pIB139, an integrative expression vector in Streptomyces [26], generating pIB139-822 (K88E) and pIB139-827 (L90K).
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