where they take care of defence (through biosynthesis of antibiotics) and detoxification of xenobiotics. The utility of these enzymes is enhanced by a broad substrate
spectrum encompassing also non-natural compounds. The down-side is their modest degree of evolution, which makes them slower by about one order of magnitude.
However, this drawback makes them highly evolvable through genetic engineering.
As shown in Fig. 1.9, enzymes from primary metabolism (A, B) are highly
optimized for their substrate and mutation predominantly produces less active
variants. In contrast, the soft fitness landscape of enzymes from secondary metabolism (C, D) allows to modify their catalytic properties so as to adapt them for a
wider range of (non-natural) substrates. When proteins are within a certain range of
sequence-relationship, an overlap of catalytic activities – promiscuity (P) – can be
explored [153]. When working with wild-type organisms, it is advisable to harvest
them towards the late stage of the exponential growth phase, when the cheap carbon
source is consumed and the ‘hungry’ cells switch on their enzyme outfit from the
secondary metabolism to survive.
References
1. Goodhue CT (1982) Microb. Transform. Bioact. Compd. 1: 9
2. Roberts SM, Turner NJ, Willetts AJ, Turner MK (1995) Introduction to Biocatalysis Using
Enzymes and Micro-organisms. Cambridge University Press, Cambridge
3. Thomas JM, Harris KDM (2016) Energy Environ. Sci. 9: 687.
4. Wittcoff HA, Reuben BG, Plotkin JS (2013) Industrial Organic Chemicals, Wiley, 3rd ed.,
p. 637.
5. http://www.essentialchemicalindustry.org/the-chemical-industry/the-chemical-industry.html
accessed Nov 20, 2016.
6. OECD (2011) Future Prospects for Industrial Biotechnology, OECD Publishing, http://dx.
doi.org/10.1787/9789264126633-en; ISBN: 9789264126633 (PDF); 9789264119567 (print).
p. 24.
7. Rozzell JD (1999) Bioorg. Med. Chem. 7: 2253.
8. Baross JA, Deming JW (1983) Nature 303: 423
9. Hough DW, Danson MJ (1999) Curr. Opin. Chem. Biol. 3: 39
Mutability
Activity
A
B
C
D
P
primary
secondary
metabolism
Fig. 1.9 Catalytic activity and evolvability of enzymes from primary and secondary metabolic
pathways.
26
1 Introduction and Background Information
spectrum encompassing also non-natural compounds. The down-side is their modest degree of evolution, which makes them slower by about one order of magnitude.
However, this drawback makes them highly evolvable through genetic engineering.
As shown in Fig. 1.9, enzymes from primary metabolism (A, B) are highly
optimized for their substrate and mutation predominantly produces less active
variants. In contrast, the soft fitness landscape of enzymes from secondary metabolism (C, D) allows to modify their catalytic properties so as to adapt them for a
wider range of (non-natural) substrates. When proteins are within a certain range of
sequence-relationship, an overlap of catalytic activities – promiscuity (P) – can be
explored [153]. When working with wild-type organisms, it is advisable to harvest
them towards the late stage of the exponential growth phase, when the cheap carbon
source is consumed and the ‘hungry’ cells switch on their enzyme outfit from the
secondary metabolism to survive.
References
1. Goodhue CT (1982) Microb. Transform. Bioact. Compd. 1: 9
2. Roberts SM, Turner NJ, Willetts AJ, Turner MK (1995) Introduction to Biocatalysis Using
Enzymes and Micro-organisms. Cambridge University Press, Cambridge
3. Thomas JM, Harris KDM (2016) Energy Environ. Sci. 9: 687.
4. Wittcoff HA, Reuben BG, Plotkin JS (2013) Industrial Organic Chemicals, Wiley, 3rd ed.,
p. 637.
5. http://www.essentialchemicalindustry.org/the-chemical-industry/the-chemical-industry.html
accessed Nov 20, 2016.
6. OECD (2011) Future Prospects for Industrial Biotechnology, OECD Publishing, http://dx.
doi.org/10.1787/9789264126633-en; ISBN: 9789264126633 (PDF); 9789264119567 (print).
p. 24.
7. Rozzell JD (1999) Bioorg. Med. Chem. 7: 2253.
8. Baross JA, Deming JW (1983) Nature 303: 423
9. Hough DW, Danson MJ (1999) Curr. Opin. Chem. Biol. 3: 39
Mutability
Activity
A
B
C
D
P
primary
secondary
metabolism
Fig. 1.9 Catalytic activity and evolvability of enzymes from primary and secondary metabolic
pathways.
26
1 Introduction and Background Information