As Kessler and Witholt state: “Regulation of PHA
metabolism can take place at different levels: (1) activation
of pha gene expression due to specific environmental
signals, such as nutrient starvation; (2) activation of
the PHA synthetic enzymes by specific cell components
or metabolic intermediates; (3) inhibition of metabolic
enzymes of competing pathways and therefore enrichment
of required intermediates for PHAsynthesis; or (4) a combination
of these.” [23]. For example, during normal bacterial
growth, the -ketothiolase in Pathway I is inhibited by
free coenzyme-A coming out of the Krebs (or TCA) cycle.
But when nutrients other than carbon are limited, acetylCoA
is restricted from entering into the Krebs cycle and
the excess acetyl-CoA is channeled into PHA biosynthesis
[95]. If growth is limited for other reasons, protein synthesis
stops, which leads to high concentrations of NADH
and NADPH. This inhibits citrate synthase and isocitrate
dehydrogenase, which again slows down the Krebs cycle,
directing acetyl-CoA towards PHA synthesis [96].
The synthesis of the PHA polymer chain takes place
within the cytoplasm ofthe bacterial cell, within inclusions
known as granules – the biochemistry ofthis synthetic process
and of these granules in turn influences the properties
of the final polymer product.