BackgroundResveratrol is a plant natural product with many health-protecting effects which makes it an attractive chemical both for academic studies and industrial purposes. However, the low quantities naturally produced by plants as well as the unsustainable procedures of extraction, purification and concentration have prompted many biotechnological approaches to produce this chemical in large quantities from renewable sources. None of these approaches have considered a microbial coculture strategy to produce this compound. The aim of this study was to prove the functionality of a microbial coculture for the biosynthesis of resveratrol.ResultsIn this work, we have successfully applied a coculture system strategy comprised of two populations of Escherichia coli strains, each with a partial and complementary section of the pathway leading to the biosynthesis of the stilbene resveratrol. The first strain is a pheA knockout mutant previously engineered to excrete p-coumaric acid into the medium through the overexpression of genes encoding a tyrosine ammonia lyase from Rhodothorula glutinis, a feedback resistant 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase and a transketolase. The second strain in the coculture was engineered to express the second part of the resveratrol biosynthetic pathway through the introduction of synthetic genes encoding the 4-coumaroyl-CoA ligase from Streptomyces coelicolor A2 and the stilbene synthase either from the peanut Arachis hypogaea or the grapevine Vitis vinifera, the latter synthesized employing a gene harmonization strategy and showing better resveratrol production performance. Batch cultures were performed in mineral medium with glycerol as the sole carbon source, where a final titer of 22.6 mg/L of resveratrol was produced in 30 h.ConclusionsTo our knowledge, this is the first time that a coculture of bacterial strains is used for the biosynthesis of resveratrol from glycerol, having the potential for a greater improvement in the product yield and avoiding the use of precursors such as p-coumaric acid, yeast extract or an expensive inhibitor such as cerulenin.

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Pseudomonas chlororaphis strain ATCC 9446 is a biocontrol-related organism. We report here its draft genome sequence assembled into 35 contigs consisting of 6,783,030 bp. Genome annotation predicted a total of 6,200 genes, 6,128 coding sequences, 81 pseudogenes, 58 tRNAs, 4 noncoding RNAs (ncRNAs), and 41 frameshifted genes.

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Microbial populations can adapt to adverse environmental conditions either by appropriately sensing and responding to the changes in their surroundings or by stochastically switching to an alternative phenotypic state. Recent data point out that these two strategies can be exhibited by the same cellular system, depending on the amplitude/frequency of the environmental perturbations and on the architecture of the genetic circuits involved in the adaptation process. Accordingly, several mitigation strategies have been designed for the effective control of microbial populations in different contexts, ranging from biomedicine to bioprocess engineering. Technically, such control strategies have been made possible by the advances made at the level of computational and synthetic biology combined with control theory. However, these control strategies have been applied mostly to synthetic gene circuits, impairing the applicability of the approach to natural circuits. In this review, we argue that it is possible to expand these control strategies to any cellular system and gene circuits based on a metric derived from this information theory, i.e., mutual information (MI). Indeed, based on this metric, it should be possible to characterize the natural frequency of any gene circuits and use it for controlling gene circuits within a population of cells.