METABOLIC DIVERSITY

Extensive biological and chemical screening of our culture library allows us to create a whole range of specialised targeted collections. Any combination of bioactivities can be selected and matched to the desired physico-chemical attributes to address even the most stringent metabolite requirements - the potential is almost limitless:

targeted bioactivity profiles
metabolic dexterity - "talented" strains and high producers
high priority actives such as producers of staurosporines or leptomycins

At the heart of these targeted collections are two databases:

BioProfile holds a complete history of each culture from isolation, through bioassay screening to fermentation.
COMET provides a complete HPLC picture of a culture's metabolic creativity.

As an illustration of the power of our databases, we can identify those cultures in our collection that produce potentially novel staurosporine analogues by two simple and rapid steps. First, a search of our physico-chemical database for the highly distinctive staurosporine UV chromophore; second, a search for cultures with the correct bioactivity profile. By combining these searches we identify 45 cultures for further investigation. Taking a lateral view, if we want novel but unrelated inhibitors with a staurosporine mode of action we look for actives with the staurosporine bioactivity profile but without the characteristic staurosporine UV chromophore.

Microbial Screening's New Chemical Entity (NCE) libraries are for those clients looking for novel actives within existing therapeutic areas. NCE libraries offer a flying start with existing IP and novel actives, supported by a discovery pipeline from Day 1.

Microbial Screening' NCE libraries consist of 50 to 100 cultures with activity against a particular therapeutic target. They are derived from an initial primary screen of at least 20,000 cultures. Only those cultures producing selective and potent activity are considered; known actives are eliminated. Up to 25% of the cultures in an NCE library are advanced to fermentation to optimise production, of which half are scaled-up to provide sufficient material for completion of the isolation chemistry. A proportion of the scaled-up cultures has been progressed to preparative fractionation leading to the isolation and structure elucidation of pure metabolites.

Implicit in the creation of a new NCE library are:

Access to primary screening data on over 20,000 cultures used to construct the library.
Detailed profiles of each active culture in multiple whole organism bioassays - potency, selectivity and toxicity.
Extensive physico-chemical analysis (HPLC, PDA, MS) to facilitate dereplication and ensure novelty.

An NCE library provides not only a number of novel actives for immediate investigation, it also provides a pipeline for future discoveries.