New Metabolites From the Co-culture of Marine-Derived Actinomycete Streptomyces rochei MB037 and Fungus Rhinocladiella similis 35

Meilin Yu,Changlun Shao,Zhiyong Li,Yingxin Li,Lu Liu,Changyun Wang,Shivakumar P Banakar

doi:10.3389/fmicb.2019.00915

Abstract

Co-culture of different microbes simulating the natural state of microbial community may produce potentially new compounds because of nutrition or space competition. To mine its metabolic potential in depth, co-culture of Streptomyces rochei MB037 with a gorgonian-derived fungus Rhinocladiella similis 35 was carried out to stimulate the production of new metabolites in this study, using pure cultivation as control. Five metabolites were isolated successfully from co-culture broth, including two new fatty acids with rare nitrile group, borrelidins J and K (1 and 2), one chromone derivative as a new natural product, 7-methoxy-2,3-dimethylchromone-4-one (3), together with two known 18-membered macrolides, borrelidin (4) and borrelidin F (5). The structures of 1–3 were elucidated by using a combination of NMR and MS spectroscopy, ester hydrolysis, and optical rotation methods. Interestingly, 1 and 2 were obtained only in co-culture. Though 3 was gained from either co-culture or single culture, its production was increased significantly by co-culture. Compound 1 exhibited significant antibacterial activity against methicillin-resistant Staphylococcus aureus with a MIC value of 0.195 μg/mL.

Highlights

In nature, microbes generally exist in a community
Based on a series of screening of co-cultivation with single strain cultivation as control, significant changes in metabolites in the fermentation broth were observed in the co-culture of a gorgonian-derived fungal strain, R. similis 35 with S. rochei MB037
The actinomycete stain S. rochei MB037 and fungal strain R. similis 35 were cultured for 3 days, respectively, and cocultivated for 11 days

Summary

Introduction

Microbes generally exist in a community. One microbe may produce biological products to inhibit other microbes for limited nutrition or space competition or against pathogenic microbes. Co-culture of microorganisms which involves the cultivation of two or more microorganisms in the same confined environment may produce potentially new compounds by stimulating the silent genes or gene clusters of one partner or increase the yields of previously described metabolites. Sung et al (2017) researched increased production of three antibiotics and enhanced biological activity against the Gram positive human pathogens via co-cultures of a. Borrelidin was isolated and elucidated as a major product from a spongederived actinomycete Streptomyces rochei MB037 (Li et al, 2018). The co-culture of S. rochei MB037 and R. similis 35 stimulated the production of new metabolites successfully. We report the isolation, structural elucidation, and evaluation of biological activities of the metabolites 1–5 (Figure 1) produced by co-culture of S. rochei MB037 and R. similis 35. A plausible biosynthesis pathway for the metabolites was proposed and discussed

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Conclusion