Discovery of Uncommon Tryptophan-Containing Diketopiperazines from Aspergillus homomorphus CBS 101889 Using an Aspergillus nidulans Heterologous Expression System.

Fungal secondary metabolite (SM) biosynthetic gene clusters (BGCs) containing dimethylallyltryptophan synthases (DMATSs) produce structurally diverse prenylated indole alkaloids with wide-ranging activities that have vast potential as human therapeutics. To discover new natural products produced by DMATSs, we mined the Department of Energy Joint Genome Institute's MycoCosm database for DMATS-containing BGCs. We found a DMATS BGC in Aspergillus homomorphus CBS 101889, which also contains a nonribosomal peptide synthetase (NRPS). This BGC appeared to have a previously unreported combination of genes, which suggested the cluster might make novel SMs. We refactored this BGC with highly inducible promoters into the model fungus Aspergillus nidulans. The expression of this refactored BGC in A. nidulans resulted in the production of eight tryptophan-containing diketopiperazines, six of which are new to science. We have named them homomorphins A-F (2, 4-8). Perhaps even more intriguingly, to our knowledge, this is the first discovery of C4-prenylated tryptophan-containing diketopiperazines and their derivatives. In addition, the NRPS from this BGC is the first described that has the ability to promiscuously combine tryptophan with either of two different amino acids, in this case, l-valine or l-allo-isoleucine.

Towards a common lexicon for equity, diversity, and inclusion work in academic medicine.

Differential rewarding of work and experience has been a longtime feature of academic medicine, resulting in a series of academic disparities. These disparities have been collectively called a cultural or minority "tax," and, when considered beyond academic medicine, exist across all departments, colleges, and schools of institutions of higher learning-from health sciences to disciplines located on university campuses outside of medicine and health. A shared language can provide opportunities for those who champion this work to pool resources for larger impacts across the institution. This article aims to catalog the terms used across academic medicine disciplines to establish a common language describing the inequities experienced by Black, Latinx, American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander, Women, and other underrepresented people as well as queer, disabled, and other historically marginalized or excluded groups. These ideas are specific to academic medicine in the United States, although many can be used in academic medicine in other countries. The terms were selected by a team of experts in equity, diversity, and inclusion, (EDI) who are considered national thought leaders in EDI and collectively have over 100 years of scholarship and experience in this area.