Date of Degree
Analytical Chemistry | Biochemistry | Bioinformatics | Microbiology | Organic Chemistry | Other Chemistry
mixed microbial culture, hydroxylated fatty acids, diketopiperazines, stereochemistry, mass spectrometry, natural products chemistry
Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the metabolites identified, this project focused on a deeper exploration of fatty acids and cyclic dipeptides. This project revealed two major findings: 1. an overlooked potential interspecies signal: (R)-12-hydroxystearic acid, exchanged in a specific social context of a terrestrial MMC derived from wheatgrass, which modulated biofilm formation in marine bacteria, and 2. from the isolation of 2,5-diketopiperazines (DKPs) from MMCs, we identified a new approach to assigning their stereochemistry. While this class of molecules is well-studied, their stereochemical assignments have remained ambiguous due to a lack of reliable, sensitive, and well-established methods. Now, with electronic circular dichroism, an unprecedented assessment of DKP stereochemistry-bioactivity relationships can proceed. While microbial molecular discovery via environmentally-derived MMCs is still in its nascent stages, our findings are promising and have established a foothold in this area of research.
Domzalski, Alison Clare, "Don't Sell Them Short, There's More to Bacterial Natural Products Than Antibiotics" (2021). CUNY Academic Works.