You finished a synthetic yeast chromosome, what next? Well after the headache of that, we started to think about tidying things up in the genome to help make custom design and synthesis of chromosomes easier for the future. For this we developed Synthetic Genome Modules, logically organised minimal synthetic modules, where genes that together encode a common function in yeast are relocated into gene clusters after their deletion at their native locus. We demonstrate this concept here first with combinatorial design of a module encoding control of the cell cycle that can minimize its gene content. We then test several designs for modules encoding amino acid biosynthesis. As part of our synthetic module design, loxPsym sequences recognised by Cre recombinase are placed between all module genes, and we leverage these for a novel master regulation system we call dCreSIR. Using dCreSIR we externally control silencing of synthetic modules by targeted binding of chromatin recruiters to loxPsym sites and this leads to inhibition of local transcription. We further show that dCreSIR can go beyond modules and be used to specifically downregulate expression across an entire synthetic yeast chromosome containing loxPsym sites. Together, our work offers insights into yeast genome organisation and establishes new principles and tools for the future design and construction of modular synthetic yeast genomes.