Effective approaches to discover new microbial metabolites in a large strain library

Natural products have provided many molecules to treat and prevent illnesses in humans, animals and plants. While only a small fraction of the existing microbial diversity has been explored for bioactive metabolites, tens of thousands of molecules have been reported in the literature over the past 80 years. Thus, the main challenge in microbial metabolite screening is to avoid the re-discovery of known metabolites in a cost-effective manner. In this perspective, we report and discuss different approaches used in our laboratory over the past few years, ranging from bioactivity-based screening to looking for metabolic rarity in different datasets to deeply investigating a single Streptomyces strain. Our results show that it is possible to find novel chemistry through a limited screening effort, provided that appropriate selection criteria are in place.

Are we appropriately testing for vitamin B12 and folate deficiency?

Background: The most common reason for assessing vitamin B12 and folate status is a clinical suspicion of deficiency along with the haematological abnormality of macrocytic anaemia.However, there is often a lack of a precise clinical or haematological picture to guide the appropriate investigation of these patients. Normal haemoglobin or mean cell volumes are often found, masking the need for appropriate investigation. When abnormal haematological parameters are found, it is often a sign of advanced deficiency. In this study we investigated whether patients with haematological findings of macrocytosis and/or anaemia are appropriately investigated for vitamin B12 and folate deficiencies and whether clinicians request metabolite screening to assist with the diagnosis.Methods: This was a retrospective audit of data obtained from the laboratory information system for a six month period at a tertiary academic hospital. Adult patients with macrocytosis, anaemia or both were selected and laboratory records reviewed to determine whether they were investigated for vitamin B12 and folate deficiency.Results: Only 16.2% of patients with macrocytic anaemia, 7.8% of patients with isolated macrocytosis and 6.5% of patients with normocytic anaemia were tested for vitamin B12 and/or folate deficiency. Metabolite assays such as homocysteine and methylmalonic acid were not requested as part of a vitamin status assessment. Conclusions: In our setting, vitamin B12 and folate assessment is a diagnostic dilemma, delaying identification of potentially debilitating disease. Clinicians need to be informed about earlier investigation and of the availability of metabolite screening and their use in establishing early deficiency.

On-demand quantitative SERS bioassays facilitated by surface-tethered ratiometric probes

A robust chip-based SERS concept for quantitative on-demand metabolite screening is established.