Dunlap, C. A. | Search bioRxiv

bioRxiv2024

Characterization of widely conserved novel pigment production in Bacillus subtilis species

Bacillus subtilis is widely studied in the microbial secondary metabolite (SM) field due to its rich variety of important natural products and genetic tractability. However, identification of novel SMs and their biosynthetic gene cluster (BGCs) has become increasingly difficult, especially in Bacilli, as the tools for screening and genome mining are dependent on clear function or similarity to already known BGCs. Pigments are SMs identified by their absorption of visible light, resulting in a certain color perceived by our eyes at sufficient concentrations. Thereby, pigments provide the evidence of a BGC without knowing the sequence or function. Expanding the known repertoire of SM BGCs with novel BGCs will further reinforce identification of a broader set of BGCs by mining tools such as antiSMASH. Here, we study a pigment observed in B. subtilis soil isolate MB9_B4 on certain media. We characterize the conditions where this pigment is produced and identify the corresponding BGC using a comparative genomic approach exploiting our strain collection containing other isolates with pigment production ability. The responsible BGC carried several genes, which were annotated as parts of the tryptophan biosynthesis pathway, possibly originating from a duplication and divergence of an originally primary metabolism. Identification of the pigment gene cluster additionally lead to the discovery of additional pigment BGC carrier B. subtilis isolates, some of which were described at the earliest in 1896 under the name Bacillus aterrimus, with a name referring to a dark pigmentation (the Latin "aterrimus" meaning very black). In addition, we employed solid-state nuclear magnetic resonance and Fourier transform infrared spectroscopies to characterize the chemical groups of the pigment. This study describes the chemical and biological features of a new class of SM BGC, which we hope will serve to improve the current BGC discovery pipelines in Bacilli.

microbiology↗

bioRxiv2021

Cell-specific expression buffering promotes cell survival and cancer robustness

Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we developed an inference index (C-score) for Cell-specific Expression- BUffering (CEBU), whereby functional buffering is mediated via expression of buffering genes in specific cells and tissues in humans. By computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq, we report that C- score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results reveal CEBU as a buffering mechanism contributing to tissue homeostasis and cancer robustness in humans. Summary blurbWe unveil a genome-wide functional buffering mechanism, termed Cell-specific Expression Buffering (CEBU), whereby gene expression contributes to functional buffering in specific cell types and tissues. We link CEBU to genetic interactions, tissue homeostasis and cancer robustness.

systems biology↗