Streptomyces hygroscopicus and rapamycinicus Evaluated from a U.S. Marine Sanctuary: Biosynthetic Gene Clusters Encode Antibiotic and Chemotherapeutic Secondary Metabolites

Abstract

Cancer remains a leading cause of death worldwide. Also threatening the public is the emergence of antibiotic resistance to existing medicines. Despite the challenge to produce viable natural products to market, there continues to be a need within public health to provide new chemotherapeutic drugs such as those exhibiting cytotoxicity and tumor cell growth-inhibitory properties. As marine genomic research advances, it is apparent that marine-derived sediment harbors uniquely potent bioactive compounds compared to their terrestrial counterparts. The Streptomyces genus in particular produces more than 30% of all secondary metabolites currently approved for human health, thus harboring unexplored reservoirs of chemotherapeutic and antibiotic agents to combat emerging disease. The present study identifies the presence of Streptomyces hygroscopicus and rapamycinicus in environmental sediment at locations within the U.S. Stellwagen Bank National Marine Sanctuary (SBNMS) from 2017 to 2022. Sequencing and bioinformatics methods catalogued biosynthetic gene clusters (BGCs) that drive cytotoxic and antibiotic biochemical processes in samples collected from sites permittable and protected to fishing activity. Poisson regression models confirmed that Sites 1 and 3 had significantly higher occurrences of rapamycinicus than other sites (p < 0.01). Poisson regression models confirmed that Sites 1, 2 and 3 had significantly higher occurrence for Streptomyces hygroscopicus across sites (p < 0.05). Interestingly, permitted fishing sites showed a greater prevalence of both species. Statistical analyses showed a significant difference in aligned hits with polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs) by site and between species with hygroscopicus showing a greater quantity than rapamycinicus among Streptomyces spp. (p < 0.05; F = 4.7 > F crit).