Publications by authors named "Jean-Malo Massicard"

Covering: up to 2024.For many years, the value of complex polyketides lay in their medical properties, including their antibiotic and antifungal activities, with little consideration paid to their native functions. However, more recent evidence gathered from the study of inter-organismal interactions has revealed the influence of these metabolites upon the ecological adaptation and distribution of their hosts, as well as their modes of communication.

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Article Synopsis
  • Filamentous organisms are significant for producing bioactive natural products, making them ideal for expressing both native and engineered biosynthetic pathways.
  • A new modular system called MoClo has been developed, providing vectors and genetic components that enable the easy construction of complex genetic circuits.
  • The effectiveness of this system was validated using the β-glucuronidase reporter, and it successfully assembled a biosynthetic pathway to flavokermesic acid, a key precursor for the valuable carminic acid.
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The CRISPR/Cas system, which has been widely applied to organisms ranging from microbes to animals, is currently being adapted for use in Streptomyces bacteria. In this case, it is notably applied to rationally modify the biosynthetic pathways giving rise to the polyketide natural products, which are heavily exploited in the medical and agricultural arenas. Our aim here is to provide the potential user with a practical guide to exploit this approach for manipulating polyketide biosynthesis, by treating key experimental aspects including vector choice, design of the basic engineering components, and trouble-shooting.

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A key goal of modular polyketide synthase (PKS) engineering is to alter polyketide stereochemistry. Here we report that exchanging whole PKS modules is a more productive approach than swapping individual ketoreductase (KR) domains for introducing rare 'A2' and 'B2' stereochemistry into model polyketides, and identify four modular 'biobricks' for such synthetic biology efforts.

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