Obesity is one of the major public health problems worldwide, mainly resulting from unhealthy lifestyles and diet. Gut microbiota dysbiosis may lead to obese humans and animals. Modulating gut bacteria through probiotics or certain dietary supplements could normalize gut microbiota and subsequently alleviate obesity. The daily consumption of Fuzhuan brick tea (FBT) or its extracts has been observed to alleviate obesity in humans and experimental animals. In this study, high-fat diet (HFD)-induced obesity in mice, such as body weight gain and fat accumulation, was prevented by the consumption of Eurotium cristatum, the dominant fungus during the manufacturing and storage of FBT. The dysbiosis of gut microbiota in C57BL/6J mice was also partially normalized. E. cristatum was able to modulate both gut fungal and bacterial compositions, based on the analysis of the microbiota composition of mice fecal samples (n = 5). E. cristatum increased acetate and butyrate-producing bacteria in mouse gut. There was five times more butyrate in the fecal samples from mice fed with E. cristatum than that from untreated HFD mice. Our results suggest that E. cristatum may be used as a probiotic fungus to alleviate obesity and to modulate gut microbiota in humans beneficially.

Microbial natural product drug discovery and development has entered a new era, driven by microbial genomics and synthetic biology. Genome sequencing has revealed the vast potential to produce valuable secondary metabolites in bacteria and fungi. However, many of the biosynthetic gene clusters are silent under standard fermentation conditions. By rational screening for mutations in bacterial ribosomal proteins or RNA polymerases, ribosome engineering is a versatile approach to obtain mutants with improved titers for microbial product formation or new natural products through activating silent biosynthetic gene clusters. In this review, we discuss the mechanism of ribosome engineering and its application to natural product discovery and yield improvement in Streptomyces. Our analysis suggests that ribosome engineering is a rapid and cost-effective approach and could be adapted to speed up the discovery and development of natural product drug leads in the post-genomic era.

The global prevalence of traditional Chinese medicine stimulates the prosperous development of herb medicines, but the annual generation of massive herb residues becomes big issues about environmental pollution and waste of resources. Microbes play important roles in the circulation of substances in nature, and endophytes represent an underexplored microbial resource possessing the unique symbiotic relationship with plants, not only for discovery of secondary metabolites, but also for potential green recycling of herb residues. The recycling capacities of several endophytic strains were respectively evaluated via solid state fermentation with herb residues of commercial Huazhenghuisheng oral-liquid (HOL). Among them, Aspergillus cristatus CB10002, a probiotic fungus isolated from Chinese Fu-brick tea, was competent to recycle HOL residues for the production of medicinal valuable anthraquinones, in which four of them, especially citreorosein with significant anti-obesity activity, were first discovered in A. cristatus. Subsequent quantitative analysis showed that about 2.0 mg/g citreorosein and 7.5 mg/g total anthraquinones could be obtained after 35-day fermentation, which was very competitive and economically beneficial. Further nutritional comparisons also revealed that the recycling process indeed ameliorated the nutrients of HOL residues, and thus proposed a possibility to directly dispose the final leftovers as a compost organic fertilizer. The endophytic and probiotic fungus A. cristatus CB10002 isolated from Chinese Fu-brick tea was screened out to effectively reutilize HOL residues for the production of nine medicinal valuable anthraquinones, whose biosynthesis may be regulated by the induction of HOL residues. The competitive yields of these anthraquinones, as well as the certain composting properties of final leftovers, have made the microbial recycling of HOL residues economically beneficial. Our work demonstrated a promising applied potential of A. cristatus in reutilization of herb residues, and provided a practical strategy for sustainable and value-added microbial recycling of herb residues.

Three natural products of nonaketide biosynthetic origin, probably biosynthesized from nine molecules of malonyl-CoA, have been isolated. Herein we described the isolation and structure elucidation of huanglongmycin (HLM) A-C and identification of the putative hlm biosynthetic gene cluster from Streptomyces sp. CB09001, isolated from a karstic cave in Xiangxi, China. Albeit previously isolated, HLM A was reported for the first time to exhibit moderate cytotoxicity against A549 lung cancer cell line (IC50 = 13.8 ± 1.5 μM) and weak antibacterial activity against gram-negative clinical isolates. A putative biosynthetic pathway for HLM A, featuring a nonaketide-specific type II polyketide synthase, was proposed. It would be consistent with the isolation of HLM B and C, which are two new natural products and likely shunt metabolites during HLM A biosynthesis.

Eurotium cristatum is the dominant fungi species in Fuzhuan brick tea (FBT), which may be responsible for the color, taste, and associated health benefits. In this study, eight E. cristatum strains were first isolated from various brands of FBT in China. Six benzaldehyde derivatives 1–6 were then isolated and characterized from these FBT-derived E. cristatum, four of which were also present in the spores of E. cristatum. The anti-inflammatory activities of these benzaldehyde derivatives were evaluated in lipopolysaccharide-induced RAW264.7 cells. These compounds could inhibit the expression both of inducible nitroxide synthase and cyclooxygenase-2. Our results suggest that the benzaldehyde derivatives from E. cristatum may be at least partially responsible for the observed health benefits of FBT.