## 1 Introduction  
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]. Fibrosis, 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]. However, successful methods for treating fibrosis have been limited, and the lack of effective small-molecule medicines is one of the serious issues [4, 5]. Therefore, the search for bioactive compounds from natural resources represents an emerging pharmacological and therapeutic area in the fight against excessive fibrotic diseases. Benzopyran derivatives have been demonstrated to have considerable bioactivities, including anti-oxidative, anti-hypertensive, anti-microorganism, and anti-inflammatory properties [6, 7, 8, 9]. In our previous studies, it was shown that xiamenomycin, a benzopyran compound with the structure of \(N\)-((3, 4-dihydro-3\(S\)-hydroxy-2\(S\)-methyl-2-(4\({}^{\prime}\)\(R\)-methyl-3\({}^{\prime}\)\(S\)-pentenyl)-2\(H\)-1-benzopyran-6-yl)carbonyl)-threonine, was obtained by cultivating the mangrove-derived strain _Streptomyces xiamenensis_ 318, and it was found to have multiple biological effects toward inhibiting fibrosis, _i.e._, the inhibition of excessive lung fibrosis _in vitro_ and the attenuation of hypertrophic scars by the suppression of local inflammation, and by the reduction of the effects of mechanical stress [10, 11, 12]. The possible mechanism could be the inhibition of the mechanical stress-induced pro-fibrotic effects by suppressing proliferation, activation, and contraction of fibroblast, and inactivating focal adhesion kinase (FAK), p38, and Rho guanosine triphosphatase signaling [10, 11, 12]. During excessive fibrogenesis, the existence of self-perpetuating loops for inflammation and extracellular matrix (ECM) accumulation, which results from the inflammatory response and the mechanical forces, is closely related to formation of fibrotic diseases [13]. Xiamenmycin, aimed at the loops, has inhibitory effects on both inflammation and mechanotransduction; therefore, it may be a potential candidate for the development of new anti-fibrotic drugs. Thus, in our ongoing study, it is worthwhile to continue the chemical and pharmaceutical investigations of new benzopyran compounds. _Streptomyces_ are known as versatile producers of novel secondary metabolites from various biosynthetic pathways. The same species of _Streptomyces_ strains even if the strains originate from different ecological niches can be used to hunt for novel bioactive compounds. Not surprisingly, an affined strain of _S. xiamenensis_ 318, namely the strain M1-94P isolated from deep-sea sediments, can produce small amounts of potentially novel benzopyrans. As the secondary metabolic pathways in the microorganisms isolated from the deep sea normally remained dormant or weakly expressed under laboratory conditions, rational strain development was critical prior to extensive chemical investigation. Ribosomal engineering is a simple but practical approach for strain breeding by targeting the microbial ribosomal proteins or the subunits of RNA polymerase and has been widely used for strain improvement [14; 15; 16; 17]. This strategy was therefore adopted to either increase the production of the benzopyran compound or stimulate the biosynthesis of novel benzopyrans by activating dormant or weakly expressed secondary metabolite biosynthetic genes in the strain _S. xiamenensis_ M1-94P. First, we introduced a spontaneous rifampicin resistant (Rif) mutation in strain M1-94P, and we then conferred streptomycin resistance (Str) to the Rif mutant by introducing a mutated _rpsL_ gene.