Small molecules with big impact

Recognizing microbial hosts as key co-workers

Nature has evolved a multitude of microorganisms with very distinct features and capabilities, which render them suitable for different biotechnological applications. Key criteria for efficient small molecule production are the genetic accessibility of the used microbes, their robustness and tolerance towards bioactive compounds, and metabolic suitability for the target biosynthesis. In IBG-1, we focus on employing the robust and established amino-acid producer Corynebacterium, the especially product-tolerant Pseudomonas group, and photosynthetic Rhodobacter species as production hosts.

Engineering of microbial cell factories

To obtain compounds as diverse as organic acids, aromatics, terpenes, alkaloids, and glycolipids, we need to engineer microbial metabolic profiles according to individual production purposes. This includes the heterologous expression of metabolic modules to confer the capability for natural product synthesis but also host cell engineering for optimized substrate utilization, improved precursor supply, reduced product degradation and increased product secretion. To meet the challenges of multiplex engineering and the expression of larger gene clusters, we utilize and develop the latest cloning and expression toolkits.

Advancing synthesis

Especially for compounds with pharmacological activities, the provision of structural diversity for tuning the biological activities is desirable. The expression of different product-specific enzymes can achieve this in a plug-and-play manner – e.g., for aromatics and terpenes. Aside from total chemical synthesis, we moreover develop semi- and mutasynthesis‑based production routes. The latter strategy enables us to feed non-natural monopyrrole precursors to P. putida, which is equipped with a part of a tripyrrole biosynthesis to obtain new-to-nature agents with improved bioactivities.