Development of morphology engineering for production of bio-based chemicals / 生物工程学报

Synthetic biology and metabolic engineering have been widely used to construct microbial cell factories for efficient production of bio-based chemicals, which mainly focus on the modification and regulation of metabolic pathways. The characteristics of microorganisms themselves, e.g. morphology, have rarely been taken into consideration in the biotechnological production processes. Morphology engineering aims to control cell shapes and cell division patterns by manipulating the genes related to cell morphology, providing a new strategy for developing efficient microbial cell factories. This review summarized the proteins related to cell morphology, followed by illustrating a few examples of using morphology engineering strategies for improving production of bio-based chemicals. This includes increasing intracellular product accumulation by regulating cell size, enhancing extracellular secretion of target products by improving cell permeability, reducing production cost by achieving high cell density, and improving product performance by controlling the degree of product hydrolysis. Finally, challenges and perspectives for the development of morphology engineering were discussed.

Dosage compensation and sex determination in Drosophila: mechanism of measurement of the X/A ratio.

We propose a molecular mechanism for the intra-cellular measurement of the ratio of the number of X chromosomes to the number of sets of autosomes, a process central to both sex determination and dosage compensation in Drosophila melanogaster. In addition to the two loci, da and Sxl, which have been shown by Cline (Genetics, 90, 683, 1978)and others to be involved in these processes, we postulate two other loci, one autosomal (ω) and the other, X-linked (π). The product of the autosomal locus da stimulates ω and initiates synthesis of a limited quantity of repressor. Sxl and π ,both of which are X-linked, compete for this repressor as well as for RNA polymerase. It is assumed that Sxl has lower affinity than π for repressor as well as polymerase and that the binding of polymerase to one of these sites modulates the binding affinity of the other site for the enzyme. It can be shown that as a result of these postulated interactions transcription from the Sxl site is proportional to the X/A ratio such that the levels of Sxl+ product are low in males, high in females and intermediate in the intersexes. If, as proposed by Cline, the Sxl- product is an inhibitor of X chromosome activity, this would result in dosage compensation. The model leads to the conclusion that high levels of Sxl+ product promote a female phenotype and low levels, a male phenotype. One interesting consequence of the assumptions on which the model is based is that the level of Sxl+ product in the cell, when examined as a function of increasing repressor concentration, first goes up and then decreases, yielding a bell-shaped curve. This feature of the model provides an explanation for some of the remarkable interactions among mutants at the Sxl, da and mle loci and leads to several predictions. The proposed mechanism may also have relevance to certain other problems, such as size regulation during development, which seem to involve measurement of ratios at the cellular level.