Cryptic Bioactive Microbial Natural Products

An untapped potential for new bioactive chemical entities

Studies of microbial genomes have revealed an overwhelming biosynthetic potential for the production of new natural compounds [1-3]. The majority of these bioinformatically identified microbial gene clusters are not expressed under normal laboratory conditions, which represent a treasure trove for the discovery of novel bioactive natural compounds [4].

Yet, microbial genome sequencing has prohibitive prices for high throughput screening, the predicted new chemical scafolds have unpredictable bioactivity, and it does not solve another main problem: these cryptic gene clusters still need to be induced.

Most natural products from microbial sources, such like fungi, are cryptic/not produced in traditional culture conditions

ENDOBIOS: AWAKENING microbial-derived natural products

One of our core proprietary approach is the disruptive induction of natural compounds codified in diverse microorganisms, such as bacteria, fungi, microalgae. These compounds were chemically refined for millions of years, the vast majority of which remain silent in their genome.

Our proprietary induction methods:

a) Relies on proprietary elicitor mechanisms – maximum of two elicitor conditions per strain;

b) Only those with induced bioactivity are selected (compared with non-induced/standard  cultures);

c) Are intended for high-throughput screening and are cost-effective;

d) Are independent from genome sequencing;

e) Can be applied to any microorganism culturable in the lab;

f) We have demonstrated the power of the approach by applying it to diverse bacteria and fungi for the discovery of new antibiotics against Gram-negative bacterial pathogens. Further, the holistic approach was already used to designed induction screening platforms to search for antifungals and also cryptic compounds against central nervous system disorders.

Isolation of environmental bacteria

References

  1. Hopwood, D., American Society for Microbiology, 2008.
  2. Cimermancic, P., et al., Cell, 2014. 158(2): p. 412-421.
  3. Katz, L. and R.H. Baltz, J Ind Microbiol Biotechnol, 2016. 43(2-3): p. 155-76.
  4. Okada, B.K. and M.R. Seyedsayamdost, FEMS Microbiol Rev, 2017. 41(1): p. 19-33.