Heterotrophic marine bacteria utilize and recycle dissolved organic matter (DOM), impacting biogeochemical cycles. It is currently unclear to what extent different DOM components can be utilized by different heterotrophic clades. Here, we ask how a natural microbial community responds to macromolecular pools that comprise much of the biomass of living organisms, and are expected to be released upon death as DOM. Surface seawater from the Eastern Mediterranean were amended with 6 defined media comprising either peptides, amino acids, amino sugars, oligosaccharides, mono sugars or organic acids. These were compared to control un-amended seawater and to seawater amended only with inorganic nutrients (N+P: NH4 and PO4). Total bacterial counts and productivity increased after 24 hours for all treatments except the control, but glucose and ATP uptake were more variable. The control and N+P were mostly dominated by Alphaproteobacteria, while the macromolecular pools additions were dominated by Gammaproteobacteria. Several families specifically increased in some treatments: peptides promoted a relative increase in Pseudoalteromonadaceae, oligosaccharides promoted both Pseudoalteromonadaceae and Alteromonadaceae, and most other treatments were dominated by Vibrionaceae, especially amino acids and amino sugars. While some results were consistent with laboratory experiments, for example Pseudoalteromonadaceae favoring peptides, other clades behaved differently. Alteromonadaceae, for example, grew well in the lab on many substrates but dominated in the field only when oligosaccharides were added. These results highlight the diversity in DOM utilization among heterotrophic bacteria and complexities in the response of natural communities, where community composition may be influenced by other factors such as competition.