Correct answer: (3) combinatorial biosynthesis

In Actinomycetes, novel polyketide structures are most effectively generated by recombining and mixing polyketide synthase (PKS) modules and tailoring genes – this strategy is called combinatorial biosynthesis and is a classic exam keyword for “novel groups of polyketides”.

Option-wise explanation:

1. Gene rearrangement

• Random gene rearrangements can occur naturally or be induced, but by themselves they are not a defined, controlled strategy to design new families of polyketides.

• This term is too vague and not the standard name of the method used for rational creation of novel polyketides.

2. Gene amplification

• Gene amplification increases the copy number of an existing biosynthetic gene cluster.

• This typically boosts the yield of an already known polyketide, but does not systematically create new structural families.

• So it is useful for overproduction, not for generating “novel groups” in the sense asked here.

3. Combinatorial biosynthesis

• This is the correct answer.

• In combinatorial biosynthesis, domains, modules or entire PKS genes from different polyketide pathways are recombined, swapped or mixed to construct “hybrid” PKS assembly lines.

• Because PKSs are modular, changing the order or identity of modules changes the sequence of extender units and reductions, giving rise to new polyketide backbones and hence novel polyketide groups.

• This strategy has been widely used in Actinomycetes (especially Streptomyces) to obtain new antibiotics and lead molecules.

4. Metabolic engineering

• Metabolic engineering optimizes fluxes of precursors, cofactors, and regulation to improve titer, yield or productivity of natural or slightly modified products.

• It can contribute to novel analog production when combined with pathway engineering, but exam questions that specifically mention “novel groups of polyketides in Actinomycetes” are classically keyed to “combinatorial biosynthesis”, not generic metabolic engineering.