Towards Precision Engineering of Canonical Polyketide Synthase Domains: Recent Advances and Future Prospects

Modular polyketide synthases (mPKSs) build functionalized polymeric chains, some of which have become blockbuster therapeutics. Organized into repeating clusters (modules) of independently-folding domains, these assembly-line-like megasynthases can be engineered by introducing non-native components. However, poor introduction points and incompatible domain combinations can cause both unintended products and dramatically reduced activity. This limits the engineering and combinatorial potential of mPKSs, precluding access to further potential therapeutics. Different regions on a given mPKS domain determine how it interacts both with its substrate and with other domains. Within the assembly line, these interactions are crucial to the proper ordering of reactions and efficient polyketide construction. Achieving control over these domain functions, through precision engineering at key regions, would greatly expand our catalogue of accessible polyketide products. Canonical mPKS domains, given that they are among the most well-characterized, are excellent candidates for such fine-tuning. The current minireview summarizes recent advances in the mechanistic understanding and subsequent precision engineering of canonical mPKS domains, focusing largely on developments in the past year..

Media Type:

Electronic Article

Year of Publication:

2017

Publication:

2017

Contained In:

To Main Record - volume:22

Contained In:

Molecules - 22(2017), 2, p 235

Language:

English

Contributors:

Carmen L. Bayly [Author]
Vikramaditya G. Yadav [Author]

Links:

doi.org [kostenfrei]
doaj.org [kostenfrei]
www.mdpi.com [kostenfrei]
Journal toc [kostenfrei]

Keywords:

Antibiotics
Organic chemistry
Polyketide synthases
Protein engineering
Structural biology
Synthetic biology

doi:

10.3390/molecules22020235

funding:

Supporting institution / Project title:

PPN (Catalogue-ID):

DOAJ010494596