Covering: 1999–2003 Marine invertebrates and a growing number of marine bacteria are the sources of novel, bioactive secondary metabolites. Structurally, many of these compounds appear to be biosynthesized by polyketide synthases (PKS) and/or nonribosomal peptide synthetases (NRPS) that have also been found in terrestrial microbes. This review highlights scientific advances from 1999–2003 in the emerging field of molecular genetics of polyketide and nonribosomal peptide natural products isolated from marine organisms. The implications of this research towards the development of marine secondary metabolites as a sustainable source of new drugs are discussed.

Acacia hydaspica R. Parker is known for its medicinal uses in multiple ailments. In this study, we performed bioassay-guided fractionation of cytotoxic compounds from A. hydaspica and investigated their effects on growth and signaling activity in prostate and breast cancer cell lines. Four active polyphenolic compounds were identified as 7-O-galloyl catechin (GC), catechin (C), methyl gallate (MG), and catechin-3-O-gallate (CG). The four compounds inhibited prostate cancer PC-3 cell growth in a dose-dependent manner, whereas CG and MG inhibited breast cancer MDA-MB-231 cell growth. All tested compounds inhibited cell survival and colony growth in both cell lines, and there was evidence of chromatin condensation, cell shrinkage and apoptotic bodies. Further, acridine orange, ethidium bromide, propidium iodide and DAPI staining demonstrated that cell death occurred partly via apoptosis in both PC-3 and MDA-MB-231 cells. In PC-3 cells treatment repressed the expression of anti-apoptotic molecules Bcl-2, Bcl-xL and survivin, coupled with down-regulation of signaling pathways AKT, NFκB, ERK1/2 and JAK/STAT. In MDA-MB-231 cells, treatment induced reduction of CK2α, Bcl-xL, survivin and xIAP protein expression along with suppression of NFκB, JAK/STAT and PI3K pathways. Our findings suggest that certain polyphenolic compounds derived from A. hydaspica may be promising chemopreventive/therapeutic candidates against cancer.

Though traditionally perceived as weapons, antibiotics are also hypothesized to act as microbial signals in natural habitats. However, while subinhibitory concentrations of antibiotics (SICA) are known to shift bacterial gene expression, specific hypotheses as to how SICA influence the ecology of natural populations are scarce. We explored whether antibiotic ‘signals’, or SICA, have the potential to alter nutrient utilization, niche overlap, and competitive species interactions among Streptomyces populations in soil. For nine diverse Streptomyces isolates, we evaluated nutrient utilization patterns on 95 different nutrient sources in the presence and absence of subinhibitory concentrations of five antibiotics. There were significant changes in nutrient use among Streptomyces isolates, including both increases and decreases in the capacity to use individual nutrients in the presence vs. in the absence of SICA. Isolates varied in their responses to SICA and antibiotics varied in their effects on isolates. Furthermore, for some isolate-isolate-antibiotic combinations, competition-free growth (growth for an isolate on all nutrients that were not utilized by a competing isolate), was increased in the presence of SICA, reducing the potential fitness cost of nutrient competition among those competitors. This suggests that antibiotics may provide a mechanism for bacteria to actively minimize niche overlap among competitors in soil. Thus, in contrast to antagonistic coevolutionary dynamics, antibiotics as signals may mediate coevolutionary displacement among coexisting Streptomyces, thereby hindering the emergence of antibiotic resistant phenotypes. These results contribute to our broad understanding of the ecology and evolutionary biology of antibiotics and microbial signals in nature.