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Succulence and leaf thickness are important anatomical traits in CAM plants, resulting from the presence of large vacuoles to store organic acids accumulated overnight. A higher degree of succulence can result in a reduction in intercellular air space which constrains internal conductance to CO2. Thus, succulence presents a trade-off between the optimal anatomy for CAM and the internal structure ideal for direct C-3 photosynthesis. This study examined how plasticity for the reversible engagement of CAM in the genus Clusia could be accommodated by leaf anatomical traits that could facilitate high nocturnal PEPC activity without compromising the direct day-time uptake of CO2 via Rubisco. Nine species of Clusia ranging from constitutive C-3 through C-3/CAM intermediates to constitutive CAM were compared in terms of leaf gas exchange, succulence, specific leaf area, and a range of leaf anatomical traits (% intercellular air space (IAS), length of mesophyll surface exposed to IAS per unit area, cell size, stomatal density/size). Relative abundances of PEPC and Rubisco proteins in different leaf tissues of a C-3 and a CAM-performing species of Clusia were determined using immunogold labelling. The results indicate that the relatively well-aerated spongy mesophyll of Clusia helps to optimize direct C-3-mediated CO2 fixation, whilst enlarged palisade cells accommodate the potential for C-4 carboxylation and nocturnal storage of organic acids. The findings provide insight on the optimal leaf anatomy that could accommodate the bioengineering of inducible CAM into C-3 crops as a means of improving water use efficiency without incurring detrimental consequences for direct C-3-mediated photosynthesis.