The next logical step is to expand this paradigm to freshwater
environments, which harbor distinct environmental selection
pressures and growth conditions and to date are virtually
unexplored for their capacity to afford unique actinomycete
bacteria. Furthermore, despite several cultivation-independent
studies aimed at characterizing lake actinomycete populations,11
to the best of our knowledge few efforts (including one study
from our laboratory) have identified secondary metabolites
from freshwater-derived actinomycetes, and included in this gap
is a notable absence of studies aimed specifically at generating
anti-TB drug leads.12−14 Thus, a major focus of our antibiotic
discovery program is to study actinobacteria derived from the
Great Lakes and other freshwater bodies. We have created an
extensive library of these bacteria and their resulting secondary
metabolite fractions. A preliminary in vitro growth inhibition
screening of this fraction library against M. tuberculosis H37Rv
led to the identification of a Micromonospora sp. isolated from
Lake Michigan sediment, whose fraction exhibited submicromolar
inhibitory activity. From this strain we isolated and
characterized two novel secondary metabolites, diazaquinomycins
H and J (DAQH and DAQJ), which to our knowledge are
among the only freshwater-derived actinomycete metabolites
described to date.12,13 Further in vitro profiling suggested that
this group of diaza-anthracene antibiotics selectively targets M.
tuberculosis over other bacteria and is active against several
forms of drug-resistant TB. Herein we present the identification
and in vitro biological characterization of this unique antibiotic
class.